Single particle cryo-electron microscopy (EM) is a method for determining the 3-D structure of macromolecules from many noisy 2-D projection images of individual macromolecules whose orientations and positions are random and unknown. The problem of orientation assignment for the images motivated work on general multireference alignment. The recently introduced non-unique games framework provides a representation theoretic approach to alignment over compact groups, and offers a convex relaxation which is formulated as semidefinite programs with certificates of global optimality under certain circumstances. One of the great opportunities in cryo-EM is studying heterogeneous samples, containing two or more distinct classes or conformations of molecules. Taking advantage of this opportunity presents an algorithmic challenge: determining both the class and orientation of each particle. We generalize multireference alignment to a problem of alignment and classification, and we propose to extend non-unique games to the problem of simultaneous alignment and classification with the goal of simultaneously classifying cryo-EM images and aligning them within their respective classes.

The rapid development of active safety systems in the automotive industry and research in autonomous driving requires reliable, high-precision sensors that provide rich information about the surrounding environment and the behaviour of other road users. In practice, there is always some non-zero mounting misalignment, i.e., angular inaccuracy in a sensor\'s mounting on a vehicle. It is essential to accurately estimate and compensate for this misalignment further programmatically (in software). In the case of radars, imprecise mounting may result in incorrect/inaccurate target information, problems with the tracking algorithm, or a decrease in the power reflected from the target. Sensor misalignment should be mitigated in two ways: through the correction of an inaccurate alignment angle via the estimated value of the misalignment angle or alerting other components of the system of potential sensor degradation if the misalignment is beyond the operational range. This work analyses misalignment\'s influences on radar sensors and other system components. In the mathematically proven example of a vertically misaligned radar, pedestrian detectability dropped to one-third of the maximum range. In addition, mathematically derived heading estimation errors demonstrate the impact on data association in data fusion. The simulation results presented show that the angle of misalignment exponentially increases the risk of false track splitting. Additionally, the paper presents a comprehensive review of radar alignment techniques, mostly found in the patent literature, and implements a baseline algorithm, along with suggested key performance indicators (KPIs) to facilitate comparisons for other researchers.

BACKGROUND: Spatial transcriptomics (ST) is advancing our understanding of complex tissues and organisms. However, building a robust clustering algorithm to define spatially coherent regions in a single tissue slice and aligning or integrating multiple tissue slices originating from diverse sources for essential downstream analyses remains challenging. Numerous clustering, alignment, and integration methods have been specifically designed for ST data by leveraging its spatial information. The absence of comprehensive benchmark studies complicates the selection of methods and future method development.
RESULTS: In this study, we systematically benchmark a variety of state-of-the-art algorithms with a wide range of real and simulated datasets of varying sizes, technologies, species, and complexity. We analyze the strengths and weaknesses of each method using diverse quantitative and qualitative metrics and analyses, including eight metrics for spatial clustering accuracy and contiguity, uniform manifold approximation and projection visualization, layer-wise and spot-to-spot alignment accuracy, and 3D reconstruction, which are designed to assess method performance as well as data quality. The code used for evaluation is available on our GitHub. Additionally, we provide online notebook tutorials and documentation to facilitate the reproduction of all benchmarking results and to support the study of new methods and new datasets.
CONCLUSIONS: Our analyses lead to comprehensive recommendations that cover multiple aspects, helping users to select optimal tools for their specific needs and guide future method development.

Individuals with neuromuscular pathologies are often prescribed an ankle-foot orthosis (AFO) to improve their gait mechanics by decreasing pathological movements of the ankle and lower limb. AFOs can resist or assist excessive or absent muscular forces that lead to tripping, instability, and slow inefficient gait. However, selecting the appropriate AFO with mechanical characteristics, which limit pathological ankle motion in certain phases of the gait cycle while facilitating effective ankle movement during other phases, requires careful clinical decision-making. The aim of this study is to propose an explicit methodology for the adjustment of multi-function articulated AFOs in clinical settings. A secondary aim is to outline the evidence supporting this methodology and to identify gaps in the literature as potential areas for future research. An emerging class of AFO, the multi-function articulated AFO, offers features that permit more comprehensive, iterative, and reversible adjustments of AFO ankle alignment and resistance to ankle motion. However, no standard method exists for the application and optimization of these therapeutic devices in the clinical setting. Here we propose an evidence-guided methodology applicable to the adjustment of multi-function articulated AFOs in the clinical setting. Characteristic load-deflection curves are given to illustrate the idealized yet complex resistance-angle behavior of multi-function articulated AFOs. Research is cited to demonstrate how these mechanical characteristics can help mitigate specific pathologic ankle and knee kinematics and kinetics. Evidence is presented to support the effects of systematic adjustment of high resistance, alignable, articulated AFOs to address many typical pathomechanical patterns observed in individuals with neuromuscular disorders. The published evidence supporting most decision points of the algorithm is presented with identified gaps in the evidence. In addition, two hypothetical case examples are given to illustrate the application of the method in optimizing multi-function articulated AFOs for treating specific gait pathomechanics. This method is proposed as an evidence-guided systematic approach for the adjustment of multi-function articulated AFOs. It utilizes observed gait deviations mapped to specific changes in AFO alignment and resistance settings as a clinical tool in orthotic treatment for individuals with complex neuromuscular gait disorders.

UNASSIGNED: The purpose of this systematic review was to compare patient satisfaction patient-reported outcomes (PROMs) levels after mechanically aligned (MA) and kinematically aligned (KA) total knee arthroplasty (TKA).
UNASSIGNED: A systematic literature search following PRISMA guidelines was conducted on PubMed, Embase, Medline and Scopus to identify potentially relevant articles for this review, published from the beginning of March 2013 until the end of October 2023. Only articles reporting satisfaction after KA TKA, MA TKA or both were included, which use valid and reliable tools for the evaluation and reporting of satisfaction after TKA. Title, authors, year of publication, study design, level of evidence, follow-up period, patients\' demographic data, sample size, type of satisfaction score, postoperative satisfaction score, postoperative alignment, statistical significance, as well as other variables, were extracted for analysis. An Agency for Healthcare Research and Quality\'s (AHRQ) design-specific scale was used for assessing randomized control trials (RCTs). The nonrandomized control trials were evaluated by using the Joanna Briggs Institute\'s (JBI) Critical Appraisal Tool. The Newcastle-Ottawa Scale (NOS) was also used to assess cohort studies, while case series were evaluated using the NIH Quality Assessment Tool for Case Series Studies.
UNASSIGNED: The initial search identified 316 studies, of which 178 were considered for screening. Eleven studies completely fulfilled the inclusion criteria, including one RCT, five nonrandomized control trials/quasi-experiments, three case series, and two cohort studies. The total number of patients recruited for MA TKA was 1740. Conversely, 497 patients were enrolled for KA TKA. Five studies used the visual analogue scale (VAS) for assessing postoperative patient satisfaction, four used the Knee Society Score (KSS) 2011 version and two Likert-based types of scores. Overall, the highest mean satisfaction score of KSS 2011 was 31.5 ± 6.6 in the MA group, and 29.8 ± 80 in the KA group in four studies. All of them showed high postoperative patient satisfaction rates for both MA and KA TKA, but with no statistically significant difference between them (p > 0.05).
UNASSIGNED: Both mechanically aligned total knee arthroplasty, as well as kinematically aligned total knee arthroplasty led to high rates of postoperative patient satisfaction, with no statistically significant differences between them.
UNASSIGNED: Level III, systematic review.

UNASSIGNED: Computer-assisted surgery (CAS) during primary total knee arthroplasty (TKA) prosthesis alignment. However, literature on its use during revision TKA (rTKA) is scarce. Moreover, the effect of CAS during rTKA on rotational alignment of the prosthesis has not been described yet. The purpose of this study was to assess the effect of CAS during rTKA, focusing on the number of outliers and coronal, sagittal and rotational prosthetic alignment compared to conventional rTKA.
UNASSIGNED: A prospective cohort study comparing CAS-rTKA with a historical control group (CON-rTKA). The CAS-rTKA group (54 patients/62 knees) underwent rTKA using imageless CAS between 2012 and 2017. The CON-rTKA group (13 patients/23 knees) was operated using the conventional technique between 2002 and 2012. Postoperative alignment was measured using the EOS-2D/3D system (coronal and sagittal planes) and computed tomography scan (rotation).
UNASSIGNED: No significant differences between the CAS-rTKA and CON-rTKA groups were found for coronal and sagittal alignment regarding the mechanical angle of the leg (p = 0.08), mechanical lateral distal femoral angle (p = 0.87), mechanical medial proximal tibial angle (p = 0.40), anatomical proximal posterior tibial angle (p = 0.43) nor femoral (p = 0.80) and tibial rotation (p = 0.15). For the proportions of coronal, sagittal and rotational outliers, no significant differences were found either.
UNASSIGNED: This study showed no evidence that use of CAS during rTKA leads to improved coronal, sagittal or rotational alignment of knee prostheses or a difference of outliers between the groups.
UNASSIGNED: Level III, therapeutic.

UNASSIGNED: The purpose of this study was to assess the differences in lower limb global alignment and anatomical parameters of coronal whole-leg radiographs, which were generally used in preoperative planning for high tibial osteotomy (HTO), according to different weight-bearing standing positions.
UNASSIGNED: Between April 2021 and December 2022, 176 patients (60 males and 116 females) were investigated. Full-weight-bearing coronal whole-leg radiographs were obtained with the patella centred on the femoral condyle. Patients were divided by Kellgren-Lawrence grade (KL-0, KL-I, KL-II and KL-III) and assessed in two standing positions: legs closed and legs spread. Patients with flexion contractures or those unable to stand with full weight bearing were excluded. The mechanical distal femoral angle, medial proximal tibial angle (MPTA), femorotibial angle, joint line convergence angle, percentage weight-bearing line (%WBL) and hip-knee-ankle angle (HKAA) were measured. The Student\'s t test was used to compare the two standing positions. A p value < 0.05 indicated a statistically significant difference.
UNASSIGNED: The MPTAs of legs closed standing and legs spread standing were 84.9 ± 2.6° and 85.1 ± 2.4° in KL-0, 84.7 ± 2.0° and 84.9 ± 2.1° in KL-I and 85.0 ± 2.43° and 85.4 ± 2.4° in KL-II, respectively. There were statistically significant differences in the MPTA between the two standing positions in KL-0, KL-I and KL-II. In contrast, the %WBL and HKAA did not change regardless of the standing position. In the KL-III group, no statistical significance was observed for any of the anatomical parameters.
UNASSIGNED: Several anatomical parameters were changed between the legs closed standing and the legs spread standing positions. It was suggested that the standing position should be taken into consideration in the planning for HTO.
UNASSIGNED: Level IV, Case series with no comparison group.

Recent years have seen a dramatic increase in the number of canine genome assemblies available. Duplications are an important source of evolutionary novelty and are also prone to misassembly. We explored the duplication content of nine canine genome assemblies using both genome self-alignment and read-depth approaches. We find that 8.58% of the genome is duplicated in the canFam4 assembly, derived from the German Shepherd Dog Mischka, including 90.15% of unplaced contigs. Highlighting the continued difficulty in properly assembling duplications, less than half of read-depth and assembly alignment duplications overlap, but the mCanLor1.2 Greenland wolf assembly shows greater concordance. Further study shows the presence of multiple segments that have alignments to four or more duplicate copies. These high-recurrence duplications correspond to gene retrocopies. We identified 3,892 candidate retrocopies from 1,316 parental genes in the canFam4 assembly and find that ∼8.82% of duplicated base pairs involve a retrocopy, confirming this mechanism as a major driver of gene duplication in canines. Similar patterns are found across eight other recent canine genome assemblies, with metrics supporting a greater quality of the PacBio HiFi mCanLor1.2 assembly. Comparison between the wolf and other canine assemblies found that 92% of retrocopy insertions are shared between assemblies. By calculating the number of generations since genome divergence, we estimate that new retrocopy insertions appear, on average, in 1 out of 3,514 births. Our analyses illustrate the impact of retrogene formation on canine genomes and highlight the variable representation of duplicated sequences among recently completed canine assemblies.

Antibody sequences can be determined at 99% accuracy directly from the polypeptide product by using bottom-up proteomics techniques. Sequencing accuracy at the peptide level is limited by the isobaric residues leucine and isoleucine, incomplete fragmentation spectra in which the order of two or more residues remains ambiguous due to lacking fragment ions for the intermediate positions, and isobaric combinations of amino acids, of potentially different lengths, for example, GG = N and GA = Q. Here, we present several updates to Stitch (v1.5), which performs template-based assembly of de novo peptides to reconstruct antibody sequences. This version introduces a mass-based alignment algorithm that explicitly accounts for mass coincidence errors. In addition, it incorporates a postprocessing procedure to assign I/L residues based on secondary fragments (satellite ions, i.e., w-ions). Moreover, evidence for sequence assignments can now be directly evaluated with the addition of an integrated spectrum viewer. Lastly, input data from a wider selection of de novo peptide sequencing algorithms are allowed, now including Casanovo, PEAKS, Novor.Cloud, pNovo, and MaxNovo, in addition to flat text and FASTA. Combined, these changes make Stitch compatible with a larger range of data processing pipelines and improve its tolerance to peptide-level sequencing errors.

Background: In recent years, there has been considerable interest in prosthetic alignment techniques for total knee arthroplasty (TKA), particularly in the so-called kinematic alignment, which aims to restore the knee\'s native alignment. However, implementing this technique requires specialized instruments and procedural steps that can be laborious. This study introduces the bisector of the trochlear groove as a reliable landmark for performing the distal femoral cut while maintaining parallelism with the native femoral joint line. Methods: Three orthopedic specialists assessed 110 X-ray images of full-leg, weight-bearing lower limbs obtained from healthy individuals between January 2021 and December 2022. The bisector of the trochlear groove was identified on the X-ray images, and the angle between this bisector and the femoral joint line was measured. The consistency of these measurements across repeated assessments and different examiners was evaluated. Results: The bisector of the trochlear groove was found to be perpendicular to the femoral joint line, with a mean angle of 89.4°. The inter-rater reliability was 68% within ±1.3° from the mean, while the intra-rater reliability was 82% within ±1.5° from the mean. Conclusions: These results suggest that by performing a femoral cut perpendicular to the bisector of the trochlear groove, surgeons can inherently restore the femoral joint line of the native knee in patients where the native joint line is no longer identifiable due to the effect of osteoarthritis. This method may offer a viable and straightforward alternative to the standard surgical technique currently practiced for kinematic alignment in TKA.