High Polygenic Risk Is Associated with Earlier Initiation and Escalation of Treatment in Early Primary Open-Angle Glaucoma.

PURPOSE: To assess the association between a glaucoma polygenic risk score (PRS) and treatment outcomes in primary open-angle glaucoma. DESIGN: Prospective, observational cohort study. PARTICIPANTS: Participants from the Progression Risk of Glaucoma: Relevant SNPs with Significant Association Study were divided into a cohort with suspect glaucoma who were treatment naive at enrollment and one with early manifest and suspect glaucoma receiving treatment at enrollment. METHODS: A per-allele weighted glaucoma PRS was calculated for 1107 participants. Multivariable mixed-effects Cox proportional regression analysis assessed the association between PRS and time to commencement of intraocular pressure (IOP)-lowering therapy in 416 patients with suspect glaucoma who were treatment naive at study enrollment. Secondary analysis evaluated the association between PRS and escalation of IOP-lowering therapy among 691 patients with suspect and early manifest glaucoma who were receiving IOP-lowering therapy at enrollment. MAIN OUTCOME MEASURES: Commencement or escalation of IOP-lowering therapy. RESULTS: A higher PRS was associated with a greater risk of commencing IOP-lowering therapy within 5 years (hazard ratio [HR], 1.45 per 1 standard deviation [/SD]; 95% confidence interval [CI], 1.27-1.62; P < 0.001). Participants in the upper population-based quintile showed a 3.3 times greater risk of commencing therapy by 5 years than those in the lowest quintile (HR, 3.30; 95% CI, 1.63-6,70; P < 0.001) and a 5.4 times greater risk of commencing IOP-lowering therapy by 2 years than the those in the lowest quintile (HR, 5.45; 95% CI, 2.08-14.25; P < 0.001). A higher PRS was associated with a greater risk of treatment escalation among patients receiving treatment at enrollment (HR, 1.19/SD; 95% CI, 1.09-1.31; P < 0.001). In combined analysis of all participants, participants in the top population-based quintile were at 2.3 times greater risk of requiring initiation or escalation of IOP-lowering therapy than those in the lowest quintile (HR, 2.33; 95% CI, 1.75-3.01; P < 0.001). CONCLUSIONS: This study demonstrated novel associations between glaucoma polygenic risk and risk of commencement or escalation of IOP-lowering therapy, building on previous work highlighting the potential clinical usefulness of genetic risk stratification in glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Impact of additional genetic abnormalities at diagnosis of chronic myeloid leukemia for first-line imatinib-treated patients receiving proactive treatment intervention.

The BCR::ABL1 gene fusion initiates chronic myeloid leukemia (CML); however, evidence has accumulated from studies of highly selected cohorts that variants in other cancer-related genes are associated with treatment failure. Nevertheless, the true incidence and impact of additional genetic abnormalities (AGA) at diagnosis of chronic phase (CP)-CML is unknown. We sought to determine whether AGA at diagnosis in a consecutive imatinib-treated cohort of 210 patients enrolled in the TIDEL-II trial influenced outcome despite a highly proactive treatment intervention strategy. Survival outcomes including overall survival, progression-free survival, failure-free survival, and BCR::ABL1 kinase domain mutation acquisition were evaluated. Molecular outcomes were measured at a central laboratory and included major molecular response (MMR, BCR::ABL1 ≤0.1%IS), MR4 (BCR::ABL1 ≤0.01%IS), and MR4.5 (BCR::ABL1 ≤0.0032%IS). AGA included variants in known cancer genes and novel rearrangements involving the formation of the Philadelphia chromosome. Clinical outcomes and molecular response were assessed based on the patient's genetic profile and other baseline factors. AGA were identified in 31% of patients. Potentially pathogenic variants in cancer-related genes were detected in 16% of patients at diagnosis (including gene fusions and deletions) and structural rearrangements involving the Philadelphia chromosome (Ph-associated rearrangements) were detected in 18%. Multivariable analysis demonstrated that the combined genetic abnormalities plus the EUTOS long-term survival clinical risk score were independent predictors of lower molecular response rates and higher treatment failure. Despite a highly proactive treatment intervention strategy, first-line imatinib-treated patients with AGA had poorer response rates. These data provide evidence for the incorporation of genomically-based risk assessment for CML.

Genetic Risk Assessment of Degenerative Eye Disease (GRADE): study protocol of a prospective assessment of polygenic risk scores to predict diagnosis of glaucoma and age-related macular degeneration.

BACKGROUND: Glaucoma and age-related macular degeneration (AMD) account for a substantial portion of global blindness. Both conditions are highly heritable, with recognised monogenic and polygenic inheritance patterns. Current screening guidelines lack decisive recommendations. Polygenic risk scores (PRS) allow for cost-effective broad population risk stratification for these conditions. The predictive potential of PRS could facilitate earlier diagnosis and treatment, and prevent unnecessary vision loss. METHODS: The Genetic Risk Assessment of Degenerative Eye disease (GRADE) study is a prospective study designed to generate high-quality evidence about the feasibility of PRS to stratify individuals from the general population, enabling identification of those at highest risk of developing glaucoma or AMD. The targeted recruitment is 1000 individuals aged over 50 years, from which blood or saliva samples will be used for genotyping and an individual PRS for glaucoma and AMD will be derived. Individuals with PRS values in the bottom decile (n = 100), top decile (n = 100) and middle 80% (n = 100) for both glaucoma and AMD will undergo a detailed eye examination for glaucoma and/or AMD. DISCUSSION: The primary objective will be to compare the prevalence of glaucoma and AMD cases between low, intermediate, and high PRS risk groups. We expect to find a higher prevalence of both diseases in the high PRS risk group, as compared to the middle and low risk groups. This prospective study will assess the clinical validity of a PRS for glaucoma and AMD in the general Australian population. Positive findings will support the implementation of PRS into clinical practice.

Evaluation of a Restoration Algorithm Applied to Clipped Tibial Acceleration Signals.

Wireless accelerometers with various operating ranges have been used to measure tibial acceleration. Accelerometers with a low operating range output distorted signals and have been found to result in inaccurate measurements of peaks. A restoration algorithm using spline interpolation has been proposed to restore the distorted signal. This algorithm has been validated for axial peaks within the range of 15.0-15.9 g. However, the accuracy of peaks of higher magnitude and the resultant peaks have not been reported. The purpose of the present study is to evaluate the measurement agreement of the restored peaks using a low-range accelerometer (±16 g) against peaks sampled using a high-range accelerometer (±200 g). The measurement agreement of both the axial and resultant peaks were examined. In total, 24 runners were equipped with 2 tri-axial accelerometers at their tibia and completed an outdoor running assessment. The accelerometer with an operating range of ±200 g was used as reference. The results of this study showed an average difference of -1.40 ± 4.52 g and -1.23 ± 5.48 g for axial and resultant peaks. Based on our findings, the restoration algorithm could skew data and potentially lead to incorrect conclusions if used without caution.

Endogenous microRNA sponges: evidence and controversy.

The competitive endogenous RNA (ceRNA) hypothesis proposes that transcripts with shared microRNA (miRNA) binding sites compete for post-transcriptional control. This hypothesis has gained substantial attention as a unifying function for long non-coding RNAs, pseudogene transcripts and circular RNAs, as well as an alternative function for messenger RNAs. Empirical evidence supporting the hypothesis is accumulating but not without attracting scepticism. Recent studies that model transcriptome-wide binding-site abundance suggest that physiological changes in expression of most individual transcripts will not compromise miRNA activity. In this Review, we critically evaluate the evidence for and against the ceRNA hypothesis to assess the impact of endogenous miRNA-sponge interactions.

Integrative genomic analysis reveals cancer-associated mutations at diagnosis of CML in patients with high-risk disease.

Genomic events associated with poor outcome in chronic myeloid leukemia (CML) are poorly understood. We performed whole-exome sequencing, copy-number variation, and/or RNA sequencing for 65 patients to discover mutations at diagnosis and blast crisis (BC). Forty-six patients with chronic-phase disease with the extremes of outcome were studied at diagnosis. Cancer gene variants were detected in 15 (56%) of 27 patients with subsequent BC or poor outcome and in 3 (16%) of 19 optimal responders (P = .007). Frequently mutated genes at diagnosis were ASXL1, IKZF1, and RUNX1 The methyltransferase SETD1B was a novel recurrently mutated gene. A novel class of variant associated with the Philadelphia (Ph) translocation was detected at diagnosis in 11 (24%) of 46 patients comprising fusions and/or rearrangement of genes on the translocated chromosomes, with evidence of fragmentation, inversion, and imperfect sequence reassembly. These were more frequent at diagnosis in patients with poor outcome: 9 (33%) of 27 vs 2 (11%) of 19 optimal responders (P = .07). Thirty-nine patients were tested at BC, and all had cancer gene variants, including ABL1 kinase domain mutations in 58%. However, ABL1 mutations cooccurred with other mutated cancer genes in 89% of cases, and these predated ABL1 mutations in 62% of evaluable patients. Gene fusions not associated with the Ph translocation occurred in 42% of patients at BC and commonly involved fusion partners that were known cancer genes (78%). Genomic analysis revealed numerous relevant variants at diagnosis in patients with poor outcome and all patients at BC. Future refined biomarker testing of specific variants will likely provide prognostic information to facilitate a risk-adapted therapeutic approach.

Does attention switching between multiple tasks affect gait stability and task performance differently between younger and older adults?

Gait stability and secondary task performance are affected by the need to share attention when dual-tasking. Further decrements may result from the need to switch attention between multiple secondary tasks. The aim of the current study was to determine the effects of attention switching upon gait stability and task performance in healthy younger and older adults. Ten healthy younger and ten healthy older adults walked on a treadmill at their preferred speed during three trials including: (1) baseline walking; (2) non-switching task walking, requiring response to an auditory-spatial or visual-spatial cue presented in an expected order; and (3) switching task walking, which required response to an auditory-spatial or visual-spatial cue presented in an unexpected order. Response time and accuracy, the margin of stability in the frontal (MoSML) and sagittal planes (MoSA: anterior, MoSP: posterior), step width and step length were calculated for non-switching and switching tasks. The MoSML, MoSA, MoSP, step width and step length during non-switching and switching tasks were normalized to baseline walking. Older adults took significantly longer to respond to cues and made more errors during the switching task compared to younger adults. Younger adults took narrower steps (p < 0.01) and displayed a reduction in MoSML (p < 0.01) during the switching task compared with the non-switching task. Conversely, older adults displayed no differences in MoSML between tasks. These findings suggest that attention switching results in different task prioritization strategies in younger and older adults during walking.

Does surface slope affect dual task performance and gait? An exploratory study in younger and older adults.

An increased risk of falling is associated with changes in gait while dual-tasking. The degree to which gait stability is altered during walking is influenced by an individual's cognitive and postural capacity, and the difficulty of the presented tasks. However, it is unknown how greater walking task difficulty affects gait stability in younger and older adults when dual-tasking. The purpose of the current study was to determine the effect of walking task difficulty on gait stability in younger and older adults while performing a difficult audiospatial task. Ten younger [mean (SD) age 30.8 (6.6) years; 5 women] and 10 older [66.8 (5.7) years; 6 women] healthy adults walked on a treadmill at their preferred walking speed [younger 4.8 (0.4) ms-1, older 4.5 (0.5) ms-1) on either a level, or downhill slope both with and without responding to an audiospatial task. Step width, step width SD and mediolateral centre of mass displacement were calculated to determine changes in gait, and response time and accuracy were calculated to determine secondary task performance. Results indicated that older adults displayed a consistently greater step width (p ≤ 0.015) and maintained their mediolateral centre of mass displacement (p > 0.05) while walking downhill and responding to the audiospatial task, compared to downhill walking only. In contrast, younger adults maintained a regular step width during both level and downhill dual-tasking compared to level and downhill walking only (p > 0.05), however displayed a lower mediolateral centre of mass displacement during level dual-task walking compared to level walking only (p = 0.013). When the difficulty of the walking task was greater, older adults increased their step width, which increased their stability.

A comparison of gait stability between younger and older adults while head turning.

Head turning while walking may challenge stability by altering visual and vestibular information. Whether there are age-related changes that affect gait stability while head turning during walking remains unknown. The aim of the current study was to compare gait stability between younger and older adults immediately following a head turn while walking. Ten younger [mean (SD)] [23.4 (3.3) years] and ten older [68.8 (6.0) years] healthy adults walked on a treadmill at their preferred gait velocity and performed head turns by responding to a visual cue. The margin of stability (MoS) in the mediolateral (MoSML), anterior (MoSA) and posterior (MoSP) directions, foot placement (mean step length and width) and rotation of the head, trunk and pelvis were calculated for the four steps immediately following a cue to head turn and compared to walking only. Older adults increased their MoSML and younger adults increased their MoSP immediately following a head turn. However, older adults had a significantly greater MoSP than younger adults during this time. Older adults also had greater pelvic rotation velocity and a trend towards smaller head-on-trunk rotation compared to younger adults. Age does not compromise the stability of healthy older compared to younger adults immediately following or when completing a head turn. However, older adults may use a different motor strategy to perform a head turn to limit isolated movement of the head and the effects of a changing sensory frame of reference.

Genome-wide identification of miR-200 targets reveals a regulatory network controlling cell invasion.

The microRNAs of the miR-200 family maintain the central characteristics of epithelia and inhibit tumor cell motility and invasiveness. Using the Ago-HITS-CLIP technology for transcriptome-wide identification of direct microRNA targets in living cells, along with extensive validation to verify the reliability of the approach, we have identified hundreds of miR-200a and miR-200b targets, providing insights into general features of miRNA target site selection. Gene ontology analysis revealed a predominant effect of miR-200 targets in widespread coordinate control of actin cytoskeleton dynamics. Functional characterization of the miR-200 targets indicates that they constitute subnetworks that underlie the ability of cancer cells to migrate and invade, including coordinate effects on Rho-ROCK signaling, invadopodia formation, MMP activity, and focal adhesions. Thus, the miR-200 family maintains the central characteristics of the epithelial phenotype by acting on numerous targets at multiple levels, encompassing both cytoskeletal effectors that control actin filament organization and dynamics, and upstream signals that locally regulate the cytoskeleton to maintain cell morphology and prevent cell migration.

Assessing the gene regulatory properties of Argonaute-bound small RNAs of diverse genomic origin.

High-throughput sequencing reveals an abundance of microRNA-sized fragments derived from larger non-coding RNAs. Roles for these small RNAs in gene silencing are suggested by their co-precipitation with Argonaute, the microRNA effector protein, though the extent to which they suppress gene expression endogenously remains unclear. To address this, we used luciferase reporters to determine the endogenous functionality of small RNAs from a diverse range of sources. We demonstrate small RNAs derived from snoRNAs have the capacity to act in a microRNA-like manner, though we note the vast majority of these are bound to Argonaute at levels below that required for detectable silencing activity. We show Argonaute exhibits a high degree of selectivity for the small RNAs with which it interacts and note that measuring Argonaute-associated levels is a better indicator of function than measuring total expression. Although binding to Argonaute at sufficient levels is necessary for demonstrating microRNA functionality in our reporter assay, this alone is not enough as some small RNAs derived from other non-coding RNAs (tRNAs, rRNAs, Y-RNAs) are associated with Argonaute at very high levels yet do not serve microRNA-like roles.

lncRNAdb v2.0: expanding the reference database for functional long noncoding RNAs.

Despite the prevalence of long noncoding RNA (lncRNA) genes in eukaryotic genomes, only a small proportion have been examined for biological function. lncRNAdb, available at http://lncrnadb.org, provides users with a comprehensive, manually curated reference database of 287 eukaryotic lncRNAs that have been described independently in the scientific literature. In addition to capturing a great proportion of the recent literature describing functions for individual lncRNAs, lncRNAdb now offers an improved user interface enabling greater accessibility to sequence information, expression data and the literature. The new features in lncRNAdb include the integration of Illumina Body Atlas expression profiles, nucleotide sequence information, a BLAST search tool and easy export of content via direct download or a REST API. lncRNAdb is now endorsed by RNAcentral and is in compliance with the International Nucleotide Sequence Database Collaboration.

The relationship between sustained hamstring pain and reorganisation of somatosensory representations: a randomised, controlled study.

ABSTRACT: Recurrent hamstring injuries are highly prevalent amongst sporting populations. It has been hypothesised that pain from an initial hamstring injury may induce reorganisation of somatosensory representations that could contribute to reinjury. However, because of the cross-sectional nature of existing research, it remains unknown whether somatosensory changes are a cause or effect of pain or if they are driven by other potentially confounding factors. Here, we explored the effect of experimentally induced sustained hamstring pain on tasks that interrogate somatosensory and spatial representations. Fifty healthy participants were randomly allocated to an experimental group that performed an eccentric exercise protocol on the right hamstring to induce delayed onset muscle soreness or a control group performing a repetition-matched concentric exercise protocol. The tactile cortical representation was assessed using two-point discrimination and tactile localisation, whereas the proprioceptive representation was assessed using a left-right judgement task. Peripersonal spatial representations were assessed using an auditory localisation task. Assessments were performed at baseline and day 2. No between-group differences in tactile acuity were observed. However, improvements in left-right judgments and worsening of auditory localisation occurred in the experimental group compared with the control group. This study provides preliminary evidence showing that somatosensory changes occur in response to sustained hamstring pain. Experimentally induced, sustained hamstring pain elicited enhancements in proprioceptive processing and deficits in peripersonal spatial processing, suggesting a shift in the allocation of attentional resources from the external (peripersonal) to internal (body) environment. These findings may hold important implications for reinjury risk and rehabilitation following hamstring pain.

The welfare of ill and injured feedlot cattle: a review of the literature and implications for managing feedlot hospital and chronic pens.

By definition, ill and injured animals are on the negative valence of animal welfare. For beef cattle kept in feedlot settings, advances in cattle health management have resulted in a greater understanding and prevention of illness and injury. However, the management of cattle once they become ill and injured is an understudied area, and there are gaps in knowledge that could inform evidence-based decision-making and strengthen welfare for this population. The aim of this review is to provide a comprehensive overview of the acquired knowledge regarding ill and injured feedlot cattle welfare, focusing on existing knowledge gaps and implications for hospital and chronic pen management and welfare assurance. Ill and injured feedlot cattle consist of acutely impaired animals with short-term health conditions that resolve with treatment and chronically impaired animals with long-term health conditions that may be difficult to treat. A literature search identified 110 articles that mentioned welfare and ill and injured feedlot cattle, but the population of interest in most of these articles was healthy cattle, not ill and injured cattle. Articles about managing ill and injured cattle in specialized hospital (n = 12) or chronic (n = 2) pens were even more sparse. Results from this literature search will be used to outline the understanding of acutely and chronically ill and injured feedlot cattle, including common dispositions and welfare considerations, behavior during convalescence, and strategies for identifying and managing ill and injured cattle. Finally, by working through specific ailments common in commercial feedlot environments, we illustrate how the Five Domains Model can be used to explore feelings and experiences and subsequent welfare state of individual ill or injured feedlot cattle. Using this approach and our knowledge of current industry practices, we identify relevant animal-based outcomes and critical research questions to strengthen knowledge in this area. A better understanding of this overlooked topic will inform future research and the development of evidence-based guidelines to help producers care for this vulnerable population.

Experimental strategies for microRNA target identification.

MicroRNAs (miRNAs) are important regulators of eukaryotic gene expression in most biological processes. They act by guiding the RNAi-induced silencing complex (RISC) to partially complementary sequences in target mRNAs to suppress gene expression by a combination of translation inhibition and mRNA decay. The commonly accepted mechanism of miRNA targeting in animals involves an interaction between the 5'-end of the miRNA called the 'seed region' and the 3' untranslated region (3'-UTR) of the mRNA. Many target prediction algorithms are based around such a model, though increasing evidence demonstrates that targeting can also be mediated through sites other than the 3'-UTR and that seed region base pairing is not always required. The power and validity of such in silico data can be therefore hindered by the simplified rules used to represent targeting interactions. Experimentation is essential to identify genuine miRNA targets, however many experimental modalities exist and their limitations need to be understood. This review summarizes and critiques the existing experimental techniques for miRNA target identification.

Global analysis of the mammalian RNA degradome reveals widespread miRNA-dependent and miRNA-independent endonucleolytic cleavage.

The Ago2 component of the RNA-induced silencing complex (RISC) is an endonuclease that cleaves mRNAs that base pair with high complementarity to RISC-bound microRNAs. Many examples of such direct cleavage have been identified in plants, but not in vertebrates, despite the conservation of catalytic capacity in vertebrate Ago2. We performed parallel analysis of RNA ends (PAREs), a deep sequencing approach that identifies 5'-phosphorylated, polyadenylated RNAs, to detect potential microRNA-directed mRNA cleavages in mouse embryo and adult tissues. We found that numerous mRNAs are potentially targeted for cleavage by endogenous microRNAs, but at very low levels relative to the mRNA abundance, apart from miR-151-5p-guided cleavage of the N4BP1 mRNA. We also find numerous examples of non-miRNA-directed cleavage, including cleavage of a group of mRNAs within a CA-repeat consensus sequence. The PARE analysis also identified many examples of adenylated small non-coding RNAs, including microRNAs, tRNA processing intermediates and various other small RNAs, consistent with adenylation being part of a widespread proof-reading and/or degradation pathway for small RNAs.

Investigating interindividual variability in corticomotor reorganization during sustained hamstring pain: A randomized experimental study.

BACKGROUND: Increasing evidence suggests that pain drives maladaptive corticomotor changes that may increase susceptibility to injury and promote symptom recurrence. However, few studies have evaluated the influence of interindividual corticomotor responses to musculoskeletal pain. Existing research in this area has also been limited largely to the upper limb. This is a pertinent point, given the functional and neurophysiological differences between upper and lower limb muscles, as well as the fact that most acute sporting injuries occur in the lower limb. Accordingly, this study explored the variability of corticomotor responses to experimentally-induced sustained hamstring pain and whether specific patterns of corticomotor reorganization were associated with poorer outcomes (mechanical sensitivity, pain, or functional limitation). METHOD: Thirty-six healthy individuals participated. Following random allocation on Day 0, the experimental group performed an eccentric exercise protocol of the right hamstring muscles to induce delayed onset muscle soreness. The control group performed repetition-matched concentric exercise that did not induce soreness. Measures of mechanical sensitivity, pain, function, and corticomotor organization were collected at baseline and on Day 2. RESULTS AND CONCLUSIONS: Corticomotor responses to sustained hamstring pain were variable. Individuals who developed corticomotor facilitation in response to hamstring pain experienced greater mechanical sensitivity than those who developed corticomotor depression. These novel data could have implications for rehabilitation following lower limb pain or injury.

The Effect of Theta Burst Stimulation Over the Primary Motor Cortex on Experimental Hamstring Pain: A Randomized, Controlled Study.

Theta burst stimulation (TBS) over the primary motor cortex (M1) is an emerging technique that may have utility in the treatment of musculoskeletal pain. However, previous work exploring the analgesic effects of noninvasive brain stimulation has been limited largely to the arm or hand, despite 80% of acute musculoskeletal injuries occurring in the lower limb. This is a pertinent point, given the functional and neurophysiological differences between upper and lower limb musculature, as well as evidence suggesting that reorganization of corticomotor pathways is region-specific. This study investigated the effect of excitatory TBS on pain, function, and corticomotor organization during experimentally induced lower limb pain. Twenty-eight healthy participants attended 2 experimental sessions. On Day 0, participants completed 10 sets of 10 maximal eccentric contractions of the right hamstring muscles to induce delayed onset muscle soreness. Four consecutive blocks of either active or sham TBS were delivered on Day 2. Measures of mechanical sensitivity, pain (muscle soreness, pain intensity, pain area) function (single-leg hop distance, maximum voluntary isometric contraction, lower extremity functional scale), and corticomotor organization were recorded before and after TBS on Day 2. Pain and function were also assessed daily from Days 2 to 10. Active TBS reduced mechanical sensitivity compared to sham stimulation (P = .01). Corticomotor organization did not differ between groups, suggesting that improvements in mechanical sensitivity were not mediated by changes in M1. Subjective reports of pain intensity and function did not change following active TBS, contrasting previous reports in studies of the upper limb. PERSPECTIVE: M1 TBS reduces mechanical sensitivity associated with experimentally induced hamstring pain. Though further work is needed, these findings may hold important implications for those seeking to expedite recovery or reduce muscle sensitivity following hamstring injury.

Tracking Bilateral Lower Limb Kinematics of Distance Runners on Treadmill Using a Single Inertial Measurement Unit.

Distance running related injuries are common, and many ailments have been associated with faulty posture. Conventional measurement of running kinematics requires sophisticated motion capture system in laboratory. In this study, we developed a wearable solution to accurately predict lower limb running kinematics using a single inertial measurement unit placed on the left lower leg. The running data collected from participants was used to train a model using long short-term memory (LSTM) neural networks with an inter-subject approach that predicted lower limb kinematics with an average accuracy of 80.2%, 85.8%, and 69.4% for sagittal hip, knee and ankle joint angles respectively for the ipsilateral limb. A comparable accuracy range was observed for the contralateral limb. The average RMSE (root mean squared error) of sagittal hip, knee and ankle were 8.76°, 13.13°, and 9.67° respectively for the ipsilateral limb. Analysis of contralateral limb kinematics was performed. The model established in this study can be used as a monitoring device to track essential running kinematics in natural running environments. Besides, the wearable solution can be an integral part of a real-time gait retraining biofeedback system for injury prevention and rehabilitation.

Unveiling the Mechanism of the in Situ Formation of 3D Fiber Macroassemblies with Controlled Properties.

Electrospinning technique is well-known for the generation of different fibers. While it is a "simple" technique, it lies in the fact that the fibers are typically produced in the form of densely packed two-dimensional (2D) mats with limited thickness, shape, and porosity. The highly demanded three-dimensional (3D) fiber assemblies have been explored by time-consuming postprocessing and/or complex setup modifications. Here, we use a classic electrospinning setup to directly produce 3D fiber macrostructures only by modulating the spinning solution. Increasing solution conductivity modifies electrodynamic jet behavior and fiber assembling process; both are observed in situ using a high-speed camera. More viscous solutions render thicker fibers that own enhanced mechanical stiffness as examined by finite element analysis. We reveal the correlation between the universal solution parameters and the dimensionality of fiber assemblies, thereof, enlightening the design of more "3D spinnable" solutions that are compatible with any commercial electrospinning equipment. After a calcination step, ultralightweight ceramic fiber assemblies are generated. These inexpensive materials can clean up exceptionally large fractions of oil spillages and provide high-performance thermal insulation. This work would drive the development and scale-up production of next-generation 3D fiber materials for engineering, biomedical, and environmental applications.