Athletes who return to sport after anterior cruciate ligament reconstruction (ACLR) demonstrate persistent biomechanical and neuromuscular deficits of the knee. There is limited evidence on what ...effect a neuromuscular training (NMT) program has on knee biomechanics in a cohort of athletes with ACLR. Therefore, the primary aim of this study was to quantify the effect of an NMT program on knee biomechanics in a cohort of ACLR athletes. Second, the post-training knee biomechanics were compared between the cohort of ACLR and control athletes.
Cohort study.
Controlled laboratory setting.
Eighteen athletes with ACLR and 10 control athletes.
Neuromuscular training.
Knee kinematics and kinetics during a double-limb jump-landing task.
There were no significant interactions (P > 0.05) observed for the athletes with ACLR. However, there was a significant main effect of biomechanics testing session (P < 0.05) for knee flexion angle and moments; athletes with ACLR demonstrated greater knee flexion angle and lower knee flexion moment during the post-training biomechanics testing session. Post-training comparison between the ACLR and control athletes demonstrated no significant interactions (P > 0.05) between the groups. There was a significant main effect of group (P < 0.05) for knee frontal angle, as athletes with ACLR landed with greater knee adduction than the control athletes.
Significant improvements in knee sagittal plane biomechanical measures were observed after the NMT program by the athletes with ACLR. In addition, post-training comparison of the ACLR and control groups demonstrates comparable knee biomechanics.
Annotation of immunologic gene function in vivo typically requires the generation of knockout mice, which is time consuming and low throughput. We previously developed CHimeric IMmune Editing ...(CHIME), a CRISPR-Cas9 bone marrow delivery system for constitutive, ubiquitous deletion of single genes. Here we describe X-CHIME, four new CHIME-based systems for modular and rapid interrogation of gene function combinatorially (C-CHIME), inducibly (I-CHIME), lineage-specifically (L-CHIME) or sequentially (S-CHIME). We use C-CHIME and S-CHIME to assess the consequences of combined deletion of Ptpn1 and Ptpn2, an embryonic lethal gene pair, in adult mice. We find that constitutive deletion of both PTPN1 and PTPN2 leads to bone marrow hypoplasia and lethality, while inducible deletion after immune development leads to enteritis and lethality. These findings demonstrate that X-CHIME can be used for rapid mechanistic evaluation of genes in distinct in vivo contexts and that PTPN1 and PTPN2 have some functional redundancy important for viability in adult mice.
Today, machine-learning software is used to help make decisions that affect people's lives. Some people believe that the application of such software results in fairer decisions because, unlike ...humans, machine-learning software generates models that are not biased. Think again. Machine-learning software is also biased, sometimes in similar ways to humans, often in different ways. While fair model- assisted decision making involves more than the application of unbiased models-consideration of application context, specifics of the decisions being made, resolution of conflicting stakeholder viewpoints, and so forth-mitigating bias from machine-learning software is important and possible but difficult and too often ignored.
Abstract
With the growing availability of data within various scientific domains, generative models hold enormous potential to accelerate scientific discovery. They harness powerful representations ...learned from datasets to speed up the formulation of novel hypotheses with the potential to impact material discovery broadly. We present the Generative Toolkit for Scientific Discovery (GT4SD). This extensible open-source library enables scientists, developers, and researchers to train and use state-of-the-art generative models to accelerate scientific discovery focused on organic material design.
Abstract Background Correction of neuromuscular impairments after anterior cruciate ligament injury is vital to successful return to sport. Frontal plane knee control during landing is a common ...measure of lower-extremity neuromuscular control and asymmetries in neuromuscular control of the knee can predispose injured athletes to additional injury and associated morbidities. Therefore, this study investigated the effects of anterior cruciate ligament injury on knee biomechanics during landing. Methods Two-dimensional frontal plane video of single leg drop, cross over drop, and drop vertical jump dynamic movement trials was analyzed for twenty injured and reconstructed athletes. The position of the knee joint center was tracked in ImageJ software for 500 milliseconds after landing to calculate medio-lateral knee motion velocities and determine normal fluency, the number of times per second knee velocity changed direction. The inverse of this calculation, analytical fluency, was used to associate larger numerical values with fluent movement. Findings Analytical fluency was decreased in involved limbs for single leg drop trials ( P = 0.0018). Importantly, analytical fluency for single leg drop differed compared to cross over drop trials for involved ( P < 0.001), but not uninvolved limbs ( P = 0.5029). For involved limbs, analytical fluency values exhibited a stepwise trend in relative magnitudes. Interpretation Decreased analytical fluency in involved limbs is consistent with previous studies. Fluency asymmetries observed during single leg drop tasks may be indicative of abhorrent landing strategies in the involved limb. Analytical fluency differences in unilateral tasks for injured limbs may represent neuromuscular impairment as a result of injury.
Inhibitor discovery for emerging drug-target proteins is challenging, especially when target structure or active molecules are unknown. Here, we experimentally validate the broad utility of a deep ...generative framework trained at-scale on protein sequences, small molecules, and their mutual interactions-unbiased toward any specific target. We performed a protein sequence-conditioned sampling on the generative foundation model to design small-molecule inhibitors for two dissimilar targets: the spike protein receptor-binding domain (RBD) and the main protease from SARS-CoV-2. Despite using only the target sequence information during the model inference, micromolar-level inhibition was observed in vitro for two candidates out of four synthesized for each target. The most potent spike RBD inhibitor exhibited activity against several variants in live virus neutralization assays. These results establish that a single, broadly deployable generative foundation model for accelerated inhibitor discovery is effective and efficient, even in the absence of target structure or binder information.
Abstract Anterior superior iliac spine (ASIS) marker occlusion commonly occurs during three-dimensional (3-D) motion capture of dynamic tasks with deep hip flexion. The purpose of this study was to ...validate a universal technique to correct ASIS occlusion. 420 ms of bilateral ASIS marker occlusion was simulated in fourteen drop vertical jump (DVJ) trials ( n =14). Kinematic and kinetic hip data calculated for pelvic segments based on iliac crest (IC) marker and virtual ASIS (produced by our algorithm and a commercial virtual join) trajectories were compared to true ASIS marker tracking data. Root mean squared errors (RMSEs; mean±standard deviation) and intra-class correlations (ICCs) between pelvic tracking based on virtual ASIS trajectories filled by our algorithm and true ASIS position were 2.3±0.9° (ICC=0.982) flexion/extension, 0.8±0.2° (ICC=0.954) abduction/adduction for hip angles, and 0.40±0.17 N m (ICC=1.000) and 1.05±0.36 N m (ICC=0.998) for sagittal and frontal plane moments. RMSEs for IC pelvic tracking were 6.9±1.8° (ICC=0.888) flexion/extension, 0.8±0.3° (ICC=0.949) abduction/adduction for hip angles, and 0.31±0.13 N m (ICC=1.00) and 1.48±0.69 N m (ICC=0.996) for sagittal and frontal plane moments. Finally, the commercially-available virtual join demonstrated RMSEs of 4.4±1.5° (ICC=0.945) flexion/extension, 0.7±0.2° (ICC=0.972) abduction/adduction for hip angles, and 0.97±0.62 N m (ICC=1.000) and 1.49±0.67 N m (ICC=0.996) for sagittal and frontal plane moments. The presented algorithm exceeded the a priori ICC cutoff of 0.95 for excellent validity and is an acceptable tracking alternative. While ICCs for the commercially available virtual join did not exhibit excellent correlation, good validity was observed for all kinematics and kinetics. IC marker pelvic tracking is not a valid alternative.
Cerebral malaria (CM) affects children and adults, but brain swelling is more severe in children. To investigate features associated with brain swelling in malaria, we performed blood profiling and ...brain MRI in a cohort of pediatric and adult patients with CM in Rourkela, India, and compared them with an African pediatric CM cohort in Malawi. We determined that higher plasma Plasmodium falciparum histidine rich protein 2 (PfHRP2) levels and elevated var transcripts that encode for binding to endothelial protein C receptor (EPCR) were linked to CM at both sites. Machine learning models trained on the African pediatric cohort could classify brain swelling in Indian children CM cases but had weaker performance for adult classification, due to overall lower parasite var transcript levels in this age group and more severe thrombocytopenia in Rourkela adults. Subgrouping of patients with CM revealed higher parasite biomass linked to severe thrombocytopenia and higher Group A-EPCR var transcripts in mild thrombocytopenia. Overall, these findings provide evidence that higher parasite biomass and a subset of Group A-EPCR binding variants are common features in children and adult CM cases, despite age differences in brain swelling.
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