Gait signature changes with walking speed are similar among able-bodied young adults despite persistent individual-specific differences.

Understanding individuals' distinct movement patterns is crucial for health, rehabilitation, and sports. Recently, we developed a machine learning-based framework to show that "gait signatures" describing the neuromechanical dynamics governing able-bodied and post-stroke gait kinematics remain individual-specific across speeds. However, we only evaluated gait signatures within a limited speed range and number of participants, using only sagittal plane (i.e., 2D) joint angles. Here we characterized changes in gait signatures across a wide range of speeds, from very slow (0.3 m/s) to exceptionally fast (above the walk-to-run transition speed) in 17 able-bodied young adults. We further assessed whether 3D kinematic and/or kinetic (ground reaction forces, joint moments, and powers) data would improve the discrimination of gait signatures. Our study showed that gait signatures remained individual-specific across walking speeds: Notably, 3D kinematic signatures achieved exceptional accuracy (99.8%, confidence interval (CI): 99.1-100%) in classifying individuals, surpassing both 2D kinematics and 3D kinetics. Moreover, participants exhibited consistent, predictable linear changes in their gait signatures across the entire speed range. These changes were associated with participants' preferred walking speeds, balance ability, cadence, and step length. These findings support gait signatures as a tool to characterize individual differences in gait and predict speed-induced changes in gait dynamics.

A systematic review of diagnostic and interventional techniques in non-occlusive hepatic artery hypoperfusion syndrome.

OBJECTIVE: This systematic review aims to elucidate the diagnostic capabilities of imaging techniques in identifying Non-Occlusive Hepatic Artery Hypoperfusion Syndrome (NOHAH) and to evaluate the efficacy and outcomes of splenic artery embolization (SAE), including the choice and placement of embolic agents. MATERIALS AND METHODS: A comprehensive literature search was conducted using PubMed, CINAHL, and Scopus databases, adhering to PRISMA guidelines. Fifteen studies encompassing 240 patients treated with embolization (using coils or Amplatzer Vascular Plugs (AVP)) were analyzed. Key metrics assessed included patient demographics, embolization techniques, embolic agents, technical success, radiologic findings pre- and post-embolization, and complication rates. RESULTS: Among the 240 patients studied, 177 (73.8%) were reported by gender, with a majority being male (127/177, 71.7%). Doppler ultrasonography (DUS) emerged as the primary initial screening tool in 80% of studies. The hepatic arterial resistive index (RI) was a critical parameter, with mean values significantly decreasing from 0.84 pre-embolization to 0.70 post-embolization (p < 0.001). All cases confirmed technical success via digital subtraction angiography, revealing delayed hepatic arterial filling without stenosis or thrombosis. Coils were the predominant embolic agent, used in 80.8% of patients, followed by AVP in 16.3%. The overall mortality rate was 4.58%, with 29 major and 3 minor complications noted. Notably, proximal placement of coils in the splenic artery was associated with lower mortality rates compared to distal placement and showed comparable complication rates to AVPs. CONCLUSION: DUS is a reliable screening modality for NOHAH, with post-SAE assessments showing significant improvements. The choice and location of embolization significantly impact patient outcomes, with proximal placement of coils emerging as a preferable strategy due to lower mortality rates and comparable complication profiles to alternative methods.

Insight into the adaptive role of arachnid genome-wide duplication through chromosome-level genome assembly of the Western black widow spider.

Although spiders are one of the most diverse groups of arthropods, the genetic architecture of their evolutionary adaptations is largely unknown. Specifically, ancient genome-wide duplication occurring during arachnid evolution ~450 mya resulted in a vast assembly of gene families, yet the extent to which selection has shaped this variation is understudied. To aid in comparative genome sequence analyses, we provide a chromosome-level genome of the Western black widow spider (Latrodectus hesperus)-a focus due to its silk properties, venom applications, and as a model for urban adaptation. We used long-read and Hi-C sequencing data, combined with transcriptomes, to assemble 14 chromosomes in a 1.46 Gb genome, with 38,393 genes annotated, and a BUSCO score of 95.3%. Our analyses identified high repetitive gene content and heterozygosity, consistent with other spider genomes, which has led to challenges in genome characterization. Our comparative evolutionary analyses of eight genomes available for species within the Araneoidea group (orb weavers and their descendants) identified 1,827 single-copy orthologs. Of these, 155 exhibit significant positive selection primarily associated with developmental genes, and with traits linked to sensory perception. These results support the hypothesis that several traits unique to spiders emerged from the adaptive evolution of ohnologs-or retained ancestrally duplicated genes-from ancient genome-wide duplication. These comparative spider genome analyses can serve as a model to understand how positive selection continually shapes ancestral duplications in generating novel traits today within and between diverse taxonomic groups.

Effects of urban-induced mutations on ecology, evolution and health.

Increasing evidence suggests that urbanization is associated with higher mutation rates, which can affect the health and evolution of organisms that inhabit cities. Elevated pollution levels in urban areas can induce DNA damage, leading to de novo mutations. Studies on mutations induced by urban pollution are most prevalent in humans and microorganisms, whereas studies of non-human eukaryotes are rare, even though increased mutation rates have the potential to affect organisms and their populations in contemporary time. Our Perspective explores how higher mutation rates in urban environments could impact the fitness, ecology and evolution of populations. Most mutations will be neutral or deleterious, and higher mutation rates associated with elevated pollution in urban populations can increase the risk of cancer in humans and potentially other species. We highlight the potential for urban-driven increased deleterious mutational loads in some organisms, which could lead to a decline in population growth of a wide diversity of organisms. Although beneficial mutations are expected to be rare, we argue that higher mutation rates in urban areas could influence adaptive evolution, especially in organisms with short generation times. Finally, we explore avenues for future research to better understand the effects of urban-induced mutations on the fitness, ecology and evolution of city-dwelling organisms.

Parents on the Concept of Physical Literacy: What Do They Know, What Do They Do, and What Do They Want?

Physical literacy development in early childhood, viewed by many as the foundation for lifelong physical activity engagement, is significantly influenced by parents. Our aim was to explore parents' understanding of physical literacy and gain insight into their perspectives on physical literacy promotion. We recruited 18 parents of children between 5 and 8 years old in Australia. Using semistructured interviews and thematic analysis, we identified several key issues regarding parents' understanding and implementation of physical literacy. Parents expressed interest in improving their implementation of physical literacy practices and had (often unintentionally) provided support for physical literacy subcomponents in the past. However, they described difficulties prioritizing physical literacy above other parental demands and expressed conflicting perceptions regarding where the responsibility should lie for developing their child's physical literacy (e.g., at home or at school). To ensure that the physical literacy "message" reaches parents, we encourage physical literacy promoters to consider the target (e.g., responsibility, priorities, and awareness) of their promotional strategies. Further investigation into the influence of sociocultural and economic factors on parents' understanding and application of physical literacy is warranted.

Efficient DNA-based data storage using shortmer combinatorial encoding.

Data storage in DNA has recently emerged as a promising archival solution, offering space-efficient and long-lasting digital storage solutions. Recent studies suggest leveraging the inherent redundancy of synthesis and sequencing technologies by using composite DNA alphabets. A major challenge of this approach involves the noisy inference process, obstructing large composite alphabets. This paper introduces a novel approach for DNA-based data storage, offering, in some implementations, a 6.5-fold increase in logical density over standard DNA-based storage systems, with near-zero reconstruction error. Combinatorial DNA encoding uses a set of clearly distinguishable DNA shortmers to construct large combinatorial alphabets, where each letter consists of a subset of shortmers. We formally define various combinatorial encoding schemes and investigate their theoretical properties. These include information density and reconstruction probabilities, as well as required synthesis and sequencing multiplicities. We then propose an end-to-end design for a combinatorial DNA-based data storage system, including encoding schemes, two-dimensional (2D) error correction codes, and reconstruction algorithms, under different error regimes. We performed simulations and show, for example, that the use of 2D Reed-Solomon error correction has significantly improved reconstruction rates. We validated our approach by constructing two combinatorial sequences using Gibson assembly, imitating a 4-cycle combinatorial synthesis process. We confirmed the successful reconstruction, and established the robustness of our approach for different error types. Subsampling experiments supported the important role of sampling rate and its effect on the overall performance. Our work demonstrates the potential of combinatorial shortmer encoding for DNA-based data storage and describes some theoretical research questions and technical challenges. Combining combinatorial principles with error-correcting strategies, and investing in the development of DNA synthesis technologies that efficiently support combinatorial synthesis, can pave the way to efficient, error-resilient DNA-based storage solutions.

Developing and testing a web-based platform for antiretroviral therapy (ART) adherence support among adolescents and young adults (AYA) living with HIV.

Objective: Describe the development and testing of a web-based platform for antiretroviral treatment (ART) adherence support among HIV+ adolescents and young adults (AYA) in a randomized controlled trial (RCT). Methods: A seven-member multi-disciplinary team operationalized the flat, password protected, web-based platform. Manualized protocols guided the objectives and content for each of the eight web-based sessions. Team members evaluated usability and content validity. Client satisfaction and perceived ease of use was evaluated with the first ten HIV+ AYA participants. Results: The web-based platform was developed, evaluated, refined, implemented and pilot tested between September 2020 to April 2022. Usability was rated as high; the evaluation of content validity showed an excellent fit between session content and objectives. HIV+ AYA participants (mean age = 24.2 years) were satisfied with the quality, type, and amount of support/education received, and found the platform easy to use, operate, and navigate. Average time spent per session was 6.5 min. Conclusion: Findings support the usability, validity, acceptability, and feasibility of this web-based platform for ART adherence support among HIV+ AYA. Innovation: Our research and findings are responsive to research gaps and the need for transparency in the methodological development and testing of web-based control arms for ART adherence support among HIV+ AYA.

MetaWin 3: open-source software for meta-analysis.

The rise of research synthesis and systematic reviews over the last 25 years has been aided by a series of software packages providing simple and accessible GUI interfaces which are intuitively easy to use by novice analysts and users. Development of many of these packages has been abandoned over time due to a variety of factors, leaving a gap in the software infrastructure available for meta-analysis. To fulfill the continued demand for a GUI-based meta-analytic system, we have now released MetaWin 3 as free, open-source, multi-platform software. MetaWin3 is written in Python and developed from scratch relative to earlier versions. The codebase is available on Github, with pre-compiled executables for both Windows and macOS available from the MetaWin website. MetaWin includes standardized effect size calculations, exploratory and publication bias analyses, and allows for both simple and complex explanatory models of variation within a meta-analytic framework, including meta-regression, using traditional least-squares/moments estimation.

Quantifying changes in individual-specific template-based representations of center-of-mass dynamics during walking with ankle exoskeletons using Hybrid-SINDy.

Ankle exoskeletons alter whole-body walking mechanics, energetics, and stability by altering center-of-mass (CoM) motion. Controlling the dynamics governing CoM motion is, therefore, critical for maintaining efficient and stable gait. However, how CoM dynamics change with ankle exoskeletons is unknown, and how to optimally model individual-specific CoM dynamics, especially in individuals with neurological injuries, remains a challenge. Here, we evaluated individual-specific changes in CoM dynamics in unimpaired adults and one individual with post-stroke hemiparesis while walking in shoes-only and with zero-stiffness and high-stiffness passive ankle exoskeletons. To identify optimal sets of physically interpretable mechanisms describing CoM dynamics, termed template signatures, we leveraged hybrid sparse identification of nonlinear dynamics (Hybrid-SINDy), an equation-free data-driven method for inferring sparse hybrid dynamics from a library of candidate functional forms. In unimpaired adults, Hybrid-SINDy automatically identified spring-loaded inverted pendulum-like template signatures, which did not change with exoskeletons (p > 0.16), except for small changes in leg resting length (p < 0.001). Conversely, post-stroke paretic-leg rotary stiffness mechanisms increased by 37-50% with zero-stiffness exoskeletons. While unimpaired CoM dynamics appear robust to passive ankle exoskeletons, how neurological injuries alter exoskeleton impacts on CoM dynamics merits further investigation. Our findings support Hybrid-SINDy's potential to discover mechanisms describing individual-specific CoM dynamics with assistive devices.

Evaluating the prescribing and monitoring of medications associated with QTc-prolongation in the ambulatory care setting.

RATIONALE: Little is known about the prescribing of medications with potential to cause QTc-prolongation in the ambulatory care settings. Understanding real-world prescribing of QTc-prolonging medications and actions taken to mitigate this risk will help guide strategies to optimize safety and appropriate prescribing among ambulatory patients. OBJECTIVE: To evaluate the frequency of clinician action taken to monitor and mitigate modifiable risk factors for QTc-prolongation when indicated. METHODS: This retrospective, cross-sectional study evaluated clinician action at the time of prescribing prespecified medications with potential to prolong QTc in adult patients in primary care. The index date was defined as the date the medication was ordered. Electronic health record (EHR) data were evaluated to assess patient, clinician and visit characteristics. Clinician action was determined if baseline or follow-up monitoring was ordered or if action was taken to mitigate modifiable risk factors (laboratory abnormalities or electrocardiogram [ECG] monitoring) within 48 h of prescribing a medication with QTc-prolonging risk. Descriptive statistics were used to describe current practice. RESULTS: A total of 399 prescriptions were prescribed to 386 patients, with a mean age of 51 ± 18 years, during March 2021 from a single-centre, multisite health system. Of these, 17 (4%) patients had a known history of QTc-prolongation, 170 (44%) did not have a documented history of QTc-prolongation and 199 (52%) had an unknown history (no ECG documented). Thirty-nine patients (10%) had at least one laboratory-related risk factor at the time of prescribing, specifically hypokalemia (16 patients), hypomagnesemia (8 patients) or hypocalcemia (19 patients). Of these 39 patients with laboratory risk factors, only 6 patients (15%) had their risk acknowledged or addressed by a clinician. Additionally, eight patients' most recent QTc was ≥500 ms and none had an ECG checked at the time the prescription was ordered. CONCLUSION: Despite national recommendations, medication monitoring and risk mitigation is infrequent when prescribing QTc-prolonging medications in the ambulatory care setting. These findings call for additional research to better understand this gap, including reasons for the gap and consequences on patient outcomes.

Trajectories of Loneliness During Adolescence Predict Subsequent Symptoms of Depression and Positive Wellbeing.

There is a need to identify the outcomes of changes in loneliness during adolescence, and to consider this within a multidimensional framework of loneliness. This study considered the effects of different trajectories of change in Isolation Loneliness and in Friendship Loneliness upon both positive wellbeing and symptoms of depression. To achieve this, 1782 (43% female; 12.92 years old at the start of the study, SD = 1.60) young people took part in a longitudinal study with four data points across 2 years. Four Isolation Loneliness trajectories and five Friendship Loneliness trajectories were identified. Youth who experienced low levels of Isolation Loneliness that subsequently increased appear to be at particular risk for poor outcomes. Similarly, initially high levels of Friendship Loneliness that decreased rapidly, or which began at a low level and only increased marginally, seem to also be a risk. Loneliness is a multi-dimensional construct and its development during adolescence impacts upon young people's depressive symptomatology and positive mental wellbeing.

A Discussion of the Contemporary Prediction Models for Atrial Fibrillation.

Atrial Fibrillation is a complex disease state with many environmental and genetic risk factors. While there are environmental factors that have been shown to increase an individual's risk of atrial fibrillation, it has become clear that atrial fibrillation has a genetic component that influences why some patients are at a higher risk of developing atrial fibrillation compared to others. This review will first discuss the clinical diagnosis of atrial fibrillation and the corresponding rhythm atrial flutter. We will then discuss how a patients' risk of stroke can be assessed by using other clinical co-morbidities. We will then review the clinical risk factors that can be used to help predict an individual patient's risk of atrial fibrillation. Many of the clinical risk factors have been used to create several different risk scoring methods that will be reviewed. We will then discuss how genetics can be used to identify individuals who are at higher risk for developing atrial fibrillation. We will discuss genome-wide association studies and other sequencing high-throughput sequencing studies. Finally, we will touch on how genetic variants derived from a genome-wide association studies can be used to calculate an individual's polygenic risk score for atrial fibrillation. An atrial fibrillation polygenic risk score can be used to identify patients at higher risk of developing atrial fibrillation and may allow for a reduction in some of the complications associated with atrial fibrillation such as cerebrovascular accidents and the development of heart failure. Finally, there is a brief discussion of how artificial intelligence models can be used to predict which patients will develop atrial fibrillation.

Nicotinamide-Expanded Allogeneic Natural Killer Cells with CD38 Deletion, Expressing an Enhanced CD38 Chimeric Antigen Receptor, Target Multiple Myeloma Cells.

Natural killer (NK) cells are a vital component of cancer immune surveillance. They provide a rapid and potent immune response, including direct cytotoxicity and mobilization of the immune system, without the need for antigen processing and presentation. NK cells may also be better tolerated than T cell therapy approaches and are susceptible to various gene manipulations. Therefore, NK cells have become the focus of extensive translational research. Gamida Cell's nicotinamide (NAM) platform for cultured NK cells provides an opportunity to enhance the therapeutic potential of NK cells. CD38 is an ectoenzyme ubiquitously expressed on the surface of various hematologic cells, including multiple myeloma (MM). It has been selected as a lead target for numerous monoclonal therapeutic antibodies against MM. Monoclonal antibodies target CD38, resulting in the lysis of MM plasma cells through various antibody-mediated mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis, significantly improving the outcomes of patients with relapsed or refractory MM. However, this therapeutic strategy has inherent limitations, such as the anti-CD38-induced depletion of CD38-expressing NK cells, thus hindering ADCC. We have developed genetically engineered NK cells tailored to treat MM, in which CD38 was knocked-out using CRISPR-Cas9 technology and an enhanced chimeric antigen receptor (CAR) targeting CD38 was introduced using mRNA electroporation. This combined genetic approach allows for an improved cytotoxic activity directed against CD38-expressing MM cells without self-inflicted NK-cell-mediated fratricide. Preliminary results show near-complete abolition of fratricide with a 24-fold reduction in self-lysis from 19% in mock-transfected and untreated NK cells to 0.8% of self-lysis in CD38 knock-out CAR NK cells. Furthermore, we have observed significant enhancements in CD38-mediated activity in vitro, resulting in increased lysis of MM target cell lines. CD38 knock-out CAR NK cells also demonstrated significantly higher levels of NK activation markers in co-cultures with both untreated and αCD38-treated MM cell lines. These NAM-cultured NK cells with the combined genetic approach of CD38 knockout and addition of CD38 CAR represent a promising immunotherapeutic tool to target MM.

Profound First-Degree Atrioventricular Block in a High-Level Basketball Athlete.

First-degree atrioventricular (AV) block (PR interval >200 ms) is commonly observed among screening electrocardiogram (ECG) in athletes. Profound first-degree AV block (PR interval >400 ms) and Mobitz type I (Wenckebach) second-degree AV block are generally uncommon and often require further workup on a case-by-case basis, particularly when there is concern for a structural cardiac abnormality. In this case, we present an example of an asymptomatic profound first-degree AV block with Mobitz type I (Wenckebach) second-degree AV block. Transthoracic echocardiogram and stress echocardiogram were unremarkable and the patient was cleared to participate in sports without any restriction. Physicians managing athletes should be aware of ECG features that require additional evaluation and cardiology consultation.

An integrated review of music cognition and rhythmic stimuli in sensorimotor neurocognition and neurorehabilitation.

This work reviews the growing body of interdisciplinary research on music cognition, using biomechanical, kinesiological, clinical, psychosocial, and sociological methods. The review primarily examines the relationship between temporal elements in music and motor responses under varying contexts, with considerable relevance for clinical rehabilitation. After providing an overview of the terminology and approaches pertinent to theories of rhythm and meter from the musical-theoretical and cognitive fields, this review focuses on studies on the effects of rhythmic sensory stimulation on gait, rhythmic cues' effect on the motor system, reactions to rhythmic stimuli attempting to synchronize mobility (i.e., musical embodiment), and the application of rhythm for motor rehabilitation for individuals with Parkinson's disease, stroke, mild cognitive impairment, Alzheimer's disease, and other neurodegenerative or neurotraumatic diseases. This work ultimately bridges the gap between the musical-theoretical and cognitive science fields to facilitate innovative research in which each discipline informs the other.

CRISPR-Cas9 engineering of the RAG2 locus via complete coding sequence replacement for therapeutic applications.

RAG2-SCID is a primary immunodeficiency caused by mutations in Recombination-activating gene 2 (RAG2), a gene intimately involved in the process of lymphocyte maturation and function. ex-vivo manipulation of a patient's own hematopoietic stem and progenitor cells (HSPCs) using CRISPR-Cas9/rAAV6 gene editing could provide a therapeutic alternative to the only current treatment, allogeneic hematopoietic stem cell transplantation (HSCT). Here we show an innovative RAG2 correction strategy that replaces the entire endogenous coding sequence (CDS) for the purpose of preserving the critical endogenous spatiotemporal gene regulation and locus architecture. Expression of the corrective transgene leads to successful development into CD3+TCRαß+ and CD3+TCRγδ+ T cells and promotes the establishment of highly diverse TRB and TRG repertoires in an in-vitro T-cell differentiation platform. Thus, our proof-of-concept study holds promise for safer gene therapy techniques of tightly regulated genes.

Discovering individual-specific gait signatures from data-driven models of neuromechanical dynamics.

Locomotion results from the interactions of highly nonlinear neural and biomechanical dynamics. Accordingly, understanding gait dynamics across behavioral conditions and individuals based on detailed modeling of the underlying neuromechanical system has proven difficult. Here, we develop a data-driven and generative modeling approach that recapitulates the dynamical features of gait behaviors to enable more holistic and interpretable characterizations and comparisons of gait dynamics. Specifically, gait dynamics of multiple individuals are predicted by a dynamical model that defines a common, low-dimensional, latent space to compare group and individual differences. We find that highly individualized dynamics-i.e., gait signatures-for healthy older adults and stroke survivors during treadmill walking are conserved across gait speed. Gait signatures further reveal individual differences in gait dynamics, even in individuals with similar functional deficits. Moreover, components of gait signatures can be biomechanically interpreted and manipulated to reveal their relationships to observed spatiotemporal joint coordination patterns. Lastly, the gait dynamics model can predict the time evolution of joint coordination based on an initial static posture. Our gait signatures framework thus provides a generalizable, holistic method for characterizing and predicting cyclic, dynamical motor behavior that may generalize across species, pathologies, and gait perturbations.

Early childhood educator outcomes from online professional development for physical literacy: A randomised controlled trial.

INTRODUCTION: Early childhood is recognised as a critical window of opportunity for physical literacy development, however early childhood educators typically lack the training required to effectively provide appropriate physical literacy opportunities for children. We examined the effects of an online physical literacy professional development program-relative to continuing with 'standard' practice-on early childhood educators' physical literacy knowledge and application. METHODS: We conducted a parallel two-arm randomised controlled trial, in which 88 early childhood educators were randomly assigned to an online professional development program designed to support educators' physical literacy instructional skills (intervention arm; n = 37), or a 'standard practice' control condition (n = 51). Data were collected prior to and after the four-week intervention period. We measured educators' physical literacy knowledge and application (our primary outcome) through independent coding of open-ended survey responses, and educators' self-reported perceptions of values, confidence, behaviours, and barriers (secondary outcomes). Between-group differences were assessed through analysis of covariance. RESULTS: One intervention arm participant withdrew from the study, resulting in 87 participants included in analysis. Educators in the intervention arm scored significantly higher on post-intervention physical literacy knowledge (d = 0.62) and application (d = 0.33) than those in the control arm. Educators in the intervention arm also scored significantly higher than controls on confidence in teaching physical activity (d = 0.42) and significantly lower than controls on perceived personal barriers to physical activity (d = 0.53). Thirteen participants in the intervention arm (36%) did not begin the online professional development program. CONCLUSION: Improvements in physical literacy instructional outcomes indicate the potential for further investigation into broader implementation of online professional development programs of this nature in the future.