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We report measurements of the polar Kerr effect, proportional to the out-of-plane component of the magnetization, in thin films of the magnetically doped topological insulator (Cr0.12Bi0.26Sb0.62)2Te3. Measurements of the complex Kerr angle ΘK were performed as a function of photon energy in the range 0.8eV< ω

While bipolar proximal femoral replacement prostheses (PFRP) have become a common treatment for tumors of the proximal femur, long-term results are not specified in the literature. The objective was to determine the complication and revision rates of bipolar PFRP and compare them to historical controls of bipolar hemiarthroplasties for nontumor indications. Information was retrospectively collected on 62 patients who received bipolar PFRP with cemented diaphyseal stems for primary or metastatic disease of the proximal femur from 1981 to 2003. Mean followup was 5 years. Twelve of 62 (19%) bipolar PFRPs underwent revision. Aseptic loosening was the most common complication with six (10%) undergoing revision. None were converted to THA due to acetabular erosion. Three patients (5%) had problems with dislocation and three (5%) had deep infections. Mean MSTS functional rating was 71% of normal function. The limb salvage rate was 98% and the 5-year event-free prosthetic survival was 79%. Bipolar PFRPs were found to have higher revision, dislocation, and deep infection rates compared to bipolar hemiarthroplasty for nontumor indications, but a lower rate of conversion to THA due to acetabular erosion. Bipolar PFRPs have good long-term durability with some complications, but are able to preserve the limb and provide good function for patients. [ABSTRACT FROM AUTHOR]

Systemic mastocytosis is characterized by clonal proliferation of mast cells, which cause disease by accumulating in various organs and releasing their chemical products into tissues. We highlight a patient with systemic mastocytosis that caused a pathologic femur fracture in a 63-year-old man with minimal trauma. The typical presentation of bone involvement is a combination of mixed sclerotic and osteolytic lesions, but this patient also had osteopenia. Although bone involvement is common in patients with systemic mastocytosis, pathologic fractures outside the vertebral column are rare. The patient was treated with intramedullary fixation of his femur and retained adequate fixation at the time of his death 7 months postoperatively. We review the literature on pathologic fractures outside the vertebral column in patients with systemic mastocytosis. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within non-Hispanic White (NHW) populations. Here we provide an extensive survey of the proteomic landscape of AD across diverse racial/ethnic groups., Methods: Two cortical regions, from multiple centers, were harmonized by uniform neuropathological diagnosis. Among 998 unique donors, 273 donors self-identified as African American, 229 as Latino American, and 434 as NHW., Results: While amyloid precursor protein and the microtubule-associated protein tau demonstrated higher abundance in AD brains, no significant race-related differences were observed. Further proteome-wide and focused analyses (specific amyloid beta [Aβ] species and the tau domains) supported the absence of racial differences in these AD pathologies within the brain proteome., Discussion: Our findings indicate that the racial differences in AD risk and clinical presentation are not underpinned by dramatically divergent patterns in the brain proteome, suggesting that other determinants account for these clinical disparities., Highlights: We present a large-scale proteome (∼10,000 proteins) of DLPFC (998) and STG (244) across AD cases. About 50% of samples were from racially and ethnically diverse brain donors. Key AD proteins (amyloid and tau) correlated with CERAD and Braak stages. No significant race-related differences in amyloid and tau protein levels were observed in AD brains. AD-associated protein changes showed a strong correlation between the brain proteomes of African American and White individuals. This dataset advances understanding of ethnoracial-specific AD pathways and potential therapies., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Ublituximab is a novel anti-CD20 monoclonal antibody glycoengineered for enhanced antibody-dependent cellular cytotoxicity. The phase 3 ULTIMATE I and II studies showed significant improvements in annualized relapse rate, total number of gadolinium-enhancing (Gd+) T1 lesions, and total number of new or enlarging T2 at Week 96, as well as improvement in the proportion of participants with no evidence of disease activity (NEDA) from Weeks 24-96 with ublituximab vs. teriflunomide., Methods: In ULTIMATE I (NCT03277261; www.clinicaltrials.gov) ( N = 549) and II (NCT03277248; www.clinicaltrials.gov) ( N = 545), participants with relapsing multiple sclerosis received ublituximab 450 mg intravenous infusion every 24 weeks (following Day 1 infusion of 150 mg and Day 15 infusion of 450 mg) or teriflunomide 14 mg oral once daily for 96 weeks. Pooled post hoc analyses evaluated NEDA by treatment epoch and participant subtype: age ( ≤ 38 or >38 years), early or later disease (<3 or ≥3 years following diagnosis), treatment history (treatment naïve or previously treated), 0 or ≥1 Gd+ T1 lesions at baseline, and Expanded Disability Status Scale score ≤ 3.5 or >3.5 at baseline. NEDA was defined as no confirmed relapses, no Gd+ T1 lesions, no new or enlarging T2 lesions, and no disability progression confirmed for ≥12 weeks., Results: NEDA rates in the ublituximab vs. teriflunomide cohorts by treatment epoch were: Weeks 0-96, 44.6% vs. 12.4% (3.6 × improvement); Weeks 24-96 (re-baselined), 82.1% vs. 22.5% (3.6 × improvement); and Weeks 48-96 (re-baselined), 88.2% vs. 30.4% (2.9 × improvement) (all p < 0.0001). The primary driver of disease activity in ublituximab-treated participants was new or enlarging T2 lesions during Weeks 0-24. 41.8% of ublituximab-treated participants who had evidence of disease activity in the first year (Weeks 0-48) experienced NEDA in the second year of treatment (Weeks 48-96) compared with 17.3% of teriflunomide-treated participants. At Weeks 24-96 (re-baselined), rates of NEDA were significantly higher with ublituximab than teriflunomide in all participant subtypes (all p < 0.0001)., Conclusions: ULTIMATE I and II pooled post hoc analyses demonstrated a consistent NEDA benefit among ublituximab-treated participants across treatment epochs and key participant subpopulations., Competing Interests: EA has received compensation for advisory boards, lectures, and consultancy with Actelion/Janssen, Alexion, Bayer, Biogen, Celgene/BMS, EMD Serono/Merck, Genentech/Roche, Genzyme, Novartis, Sanofi, and TG Therapeutics; research support from Biogen, Genentech/Roche, Novartis, TG Therapeutics, Patient-Centered Outcomes Research Initiative, National Multiple Sclerosis Society, National Institutes of Health, and Rocky Mountain MS Center. LS has received compensation for consulting from TG Therapeutics. H-PH has received honoraria for serving on steering or data monitoring committees or speaker fees from Bayer, Biogen, Boehringer Ingelheim, BMS Celgene, GeNeuro, Merck, Novartis, Sanofi, TG Therapeutics, and Roche with approval by the Rector of Heinrich-Heine-Universität. PQ has received speaking and consulting honoraria from Biogen, BMS, Genzyme, Genentech, Viela Bio, and TG Therapeutics. SW has received compensation for consulting from TG Therapeutics; has been a consultant, speaker, and research participant for Celgene/BMS, Biogen, EMD Serono, Genentech/Roche, and Genzyme/Sanofi; has conducted research/been a consultant for Novartis, and has conducted research for Alkermes and TG Therapeutics. DR has received consultancy fees from Greenwich Biosciences, Mallinckrodt, and Novartis; honoraria or speaker fees and consultancy fees from Alexion, Amgen, Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Horizon, ImmPACT Bio, Janssen, Sanofi Genzyme, and TG Therapeutics; research grant support from Anokion, Atara Biotherapeutics, Biogen, CorEvitas, EMD Serono, Genentech, GW Pharmaceuticals, Janssen, Novartis, PCORI, PRIME CME, Sanofi Genzyme, TG Therapeutics, and UCB. KS has received honoraria for speaking, consulting, and serving on advisory boards from Merck, Novartis, Roche, Biogen, Celgene, BMS, and TG Therapeutics. DW's employer has received research funding, speaking fees, or he has served as expert witness for AbbVie, Adamas, Allergan, ANI Pharma, Avanir, Banner Life, Biogen, Bristol Myers Squibb, Chugai, Eli Lilly, EMD Serono, Genentech, GW Therapeutics, Immunic, InnoCare, Janssen, Jazz Pharmaceuticals, Mallinckrodt, MAPI Therapeutics, Mylan, National MS Society, Novartis, SanBio, Sanofi Genzyme, UCB Biopharma, Viela Bio, Teva Pharmaceuticals, and TG Therapeutics and was employed by Consultants in Neurology. EF, KM, YX, KB, and HM are employees of TG Therapeutics. BC has received personal compensation for consulting from Alexion, Atara, Autobahn, Avotres, Biogen, Boston Pharma, EMD Serono, Gossamer Bio, Hexal/Sandoz, Horizon, Immunic AG, Kyverna, Neuron23, Novartis, Sanofi, Siemens, and TG Therapeutics and received research support from Genentech and Kyverna. The authors declare that this study received funding from TG Therapeutics. The funder was involved in the study design, collection, analysis, interpretation of data, the writing of this article, and the decision to submit for publication. All authors had full editorial oversight of the manuscript and provided final approval for all content. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Alvarez, Steinman, Fox, Hartung, Qian, Wray, Robertson, Selmaj, Wynn, Mok, Xu, Bodhinathan, Miskin and Cree.)

Introduction: Heparin binding proteins (HBPs) with roles in extracellular matrix assembly are strongly correlated to β-amyloid (Aβ) and tau pathology in Alzheimer's disease (AD) brain and cerebrospinal fluid (CSF). However, it remains challenging to detect these proteins in plasma using standard mass spectrometry-based proteomic approaches., Methods: We employed heparin-affinity chromatography, followed by off-line fractionation and tandem mass tag mass spectrometry (TMT-MS), to enrich HBPs from plasma obtained from AD (n = 62) and control (n = 47) samples. These profiles were then correlated to Aβ, tau and phosphorylated tau (pTau) CSF biomarkers and plasma pTau181 from the same individuals, as well as a consensus brain proteome network to assess the overlap with AD brain pathophysiology., Results: Heparin enrichment from plasma was highly reproducible, enriched well-known HBPs like APOE and thrombin, and depleted high-abundant proteins such as albumin. A total of 2865 proteins, spanning 10 orders of magnitude in abundance, were measured across 109 samples. Compared to the consensus AD brain protein co-expression network, we observed that specific plasma proteins exhibited consistent direction of change in both brain and plasma, whereas others displayed divergent changes, highlighting the complex interplay between the two compartments. Elevated proteins in AD plasma, when compared to controls, included members of the matrisome module in brain that accumulate with Aβ deposits, such as SMOC1, SMOC2, SPON1, MDK, OLFML3, FRZB, GPNMB, and the APOE4 proteoform. Additionally, heparin-enriched proteins in plasma demonstrated significant correlations with conventional AD CSF biomarkers, including Aβ, total tau, pTau, and plasma pTau181. A panel of five plasma proteins classified AD from control individuals with an area under the curve (AUC) of 0.85. When combined with plasma pTau181, the panel significantly improved the classification performance of pTau181 alone, increasing the AUC from 0.93 to 0.98. This suggests that the heparin-enriched plasma proteome captures additional variance in cognitive dementia beyond what is explained by pTau181., Conclusion: These findings support the utility of a heparin-affinity approach coupled with TMT-MS for enriching amyloid-associated proteins, as well as a wide spectrum of plasma biomarkers that reflect pathological changes in the AD brain., (© 2024. The Author(s).)

Introduction: Multi-omics studies in Alzheimer's disease (AD) revealed many potential disease pathways and therapeutic targets. Despite their promise of precision medicine, these studies lacked Black Americans (BA) and Latin Americans (LA), who are disproportionately affected by AD., Methods: To bridge this gap, Accelerating Medicines Partnership in Alzheimer's Disease (AMP-AD) expanded brain multi-omics profiling to multi-ethnic donors., Results: We generated multi-omics data and curated and harmonized phenotypic data from BA (n = 306), LA (n = 326), or BA and LA (n = 4) brain donors plus non-Hispanic White (n = 252) and other (n = 20) ethnic groups, to establish a foundational dataset enriched for BA and LA participants. This study describes the data available to the research community, including transcriptome from three brain regions, whole genome sequence, and proteome measures., Discussion: The inclusion of traditionally underrepresented groups in multi-omics studies is essential to discovering the full spectrum of precision medicine targets that will be pertinent to all populations affected with AD., Highlights: Accelerating Medicines Partnership in Alzheimer's Disease Diversity Initiative led brain tissue profiling in multi-ethnic populations. Brain multi-omics data is generated from Black American, Latin American, and non-Hispanic White donors. RNA, whole genome sequencing and tandem mass tag proteomicsis completed and shared. Multiple brain regions including caudate, temporal and dorsolateral prefrontal cortex were profiled., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Brief exposure to repeated episodes of low inspired oxygen, or acute intermittent hypoxia (AIH), is a promising therapeutic modality to improve motor function after chronic, incomplete spinal cord injury (SCI). Although therapeutic AIH is under extensive investigation in persons with SCI, limited data are available concerning cardiorespiratory responses during and after AIH exposure despite implications for AIH safety and tolerability. Thus, we recorded immediate (during treatment) and enduring (up to 30 min post-treatment) cardiorespiratory responses to AIH in 19 participants with chronic SCI (>1 year post-injury; injury levels C1 to T6; American Spinal Injury Association Impairment Scale A to D; mean age = 33.8 ± 14.1 years; 18 males). Participants completed a single AIH (15, 60-sec episodes, inspired O 2 ≈ 10%; 90-sec intervals breathing room air) and Sham (inspired O 2 ≈ 21%) treatment, in random order. During hypoxic episodes: (1) arterial oxyhemoglobin saturation decreased to 82.1 ± 2.9% ( p  < 0.001); (2) minute ventilation increased 3.83 ± 2.29 L/min ( p  = 0.008); and (3) heart rate increased 4.77 ± 6.82 bpm ( p  = 0.010). Considerable variability in cardiorespiratory responses was found among subjects; some individuals exhibited large hypoxic ventilatory responses (≥0.20 L/min/%, n  = 11), whereas others responded minimally (<0.20 L/min/%, n  = 8). Apneas occurred frequently during AIH and/or Sham protocols in multiple participants. All participants completed AIH treatment without difficulty. No significant changes in ventilation, heart rate, or arterial blood pressure were found 30 min post-AIH p  > 0.05). In conclusion, therapeutic AIH is well tolerated, elicits variable chemoreflex activation, and does not cause persistent changes in cardiorespiratory control/function 30 min post-treatment in persons with chronic SCI.

Background: Gait speed or 6-minute walk test are frequently used to project community ambulation abilities post-stroke by categorizing individuals as household ambulators, limited, or unlimited community ambulators. However, whether improved clinically-assessed gait outcomes truly translate into enhanced real-world community ambulation remains uncertain., Objective: This cross-sectional study aimed to examine differences in home and community ambulation between established categories of speed- and endurance-based classification systems of community ambulation post-stroke and compare these with healthy controls., Methods: Sixty stroke survivors and 18 healthy controls participated. Stroke survivors were categorized into low-speed, medium-speed, or high-speed groups based on speed-based classifications and into low-endurance, medium-endurance, or high-endurance groups based on the endurance-based classification. Home and community steps/day were quantified using Global Positioning System and accelerometer devices over 7 days., Results: The low-speed groups exhibited fewer home and community steps/day than their medium- and high-speed counterparts ( P   <   .05 ). The low-endurance group took fewer community steps/day than the high-endurance group ( P   <   .05 ). Despite vast differences in clinical measures of gait speed and endurance, the medium-speed/endurance groups did not differ in their home and community steps/day from the high-speed/endurance groups, respectively. Stroke survivors took 48% fewer home steps/day and 77% fewer community steps/day than healthy controls., Conclusions: Clinical classification systems may only distinguish home ambulators from community ambulators, but not between levels of community ambulation, especially beyond certain thresholds of gait speed and endurance. Clinicians should use caution when predicting community ambulation status through clinical measures, due to the limited translation of these classification systems into the real world., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Multiple lines of evidence support peripheral organs in the initiation or progression of Lewy body disease (LBD), a spectrum of neurodegenerative diagnoses that include Parkinson's Disease (PD) without or with dementia (PDD) and dementia with Lewy bodies (DLB). However, the potential contribution of the peripheral immune response to LBD remains unclear. This study aims to characterize peripheral immune responses unique to participants with LBD at single-cell resolution to highlight potential biomarkers and increase mechanistic understanding of LBD pathogenesis in humans., Methods: In a case-control study, peripheral mononuclear cell (PBMC) samples from research participants were randomly sampled from multiple sites across the United States. The diagnosis groups comprise healthy controls (HC, n = 159), LBD (n = 110), Alzheimer's disease dementia (ADD, n = 97), other neurodegenerative disease controls (NDC, n = 19), and immune disease controls (IDC, n = 14). PBMCs were activated with three stimulants (LPS, IL-6, and IFNa) or remained at basal state, stained by 13 surface markers and 7 intracellular signal markers, and analyzed by flow cytometry, which generated 1,184 immune features after gating., Results: The model classified LBD from HC with an AUROC of 0.87 ± 0.06 and AUPRC of 0.80 ± 0.06. Without retraining, the same model was able to distinguish LBD from ADD, NDC, and IDC. Model predictions were driven by pPLCγ2, p38, and pSTAT5 signals from specific cell populations under specific activation. The immune responses characteristic for LBD were not associated with other common medical conditions related to the risk of LBD or dementia, such as sleep disorders, hypertension, or diabetes., Conclusions and Relevance: Quantification of PBMC immune response from multisite research participants yielded a unique pattern for LBD compared to HC, multiple related neurodegenerative diseases, and autoimmune diseases thereby highlighting potential biomarkers and mechanisms of disease., (© 2024. The Author(s).)

In pathology, the deployment of artificial intelligence (AI) in clinical settings is constrained by limitations in data collection and in model transparency and interpretability. Here we describe a digital pathology framework, nuclei.io, that incorporates active learning and human-in-the-loop real-time feedback for the rapid creation of diverse datasets and models. We validate the effectiveness of the framework via two crossover user studies that leveraged collaboration between the AI and the pathologist, including the identification of plasma cells in endometrial biopsies and the detection of colorectal cancer metastasis in lymph nodes. In both studies, nuclei.io yielded considerable diagnostic performance improvements. Collaboration between clinicians and AI will aid digital pathology by enhancing accuracies and efficiencies., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Community ambulation involves complex walking adaptability tasks such as stepping over obstacles or taking long steps, which require adequate propulsion generation by the trailing leg. Individuals post-stroke often have an increased reliance on their trailing nonparetic leg and favor leading with their paretic leg, which can limit mobility. Ankle-foot-orthoses are prescribed to address common deficits post-stroke such as foot drop and ankle instability. However, it is not clear if walking with an ankle-foot-orthosis improves inter-limb propulsion symmetry during adaptability tasks. This study sought to examine this hypothesis., Methods: Individuals post-stroke (n = 9) that were previously prescribed a custom fabricated plantarflexion-stop articulated ankle-foot-orthosis participated. Participants performed steady-state walking and adaptability tasks overground with and without their orthosis. The adaptability tasks included obstacle crossing and long-step tasks, leading with both their paretic and nonparetic leg. Inter-limb propulsion symmetry was calculated using trailing limb ground-reaction-forces., Findings: During the obstacle crossing task, ankle-foot-orthosis use resulted in a significant improvement in inter-limb propulsion symmetry. The orthosis also improved ankle dorsiflexion during stance, reduced knee hyperextension, increased gastrocnemius muscle activity, and increased peak paretic leg ankle plantarflexor moment. In contrast, there were no differences in propulsion symmetry during steady-state walking and taking a long-step when using the orthosis., Interpretation: Plantarflexion-stop articulated ankle-foot-orthoses can improve propulsion symmetry during obstacle crossing tasks in individuals post-stroke, promoting paretic leg use and reduced reliance on the nonparetic leg., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: Cerebrovascular dysfunction is a pathological hallmark of Alzheimer's disease (AD). Nevertheless, detecting cerebrovascular changes within bulk tissues has limited our ability to characterize proteomic alterations from less abundant cell types., Methods: We conducted quantitative proteomics on bulk brain tissues and isolated cerebrovasculature from the same individuals, encompassing control (N = 28), progressive supranuclear palsy (PSP) (N = 18), and AD (N = 21) cases., Results: Protein co-expression network analysis identified unique cerebrovascular modules significantly correlated with amyloid plaques, cerebrovascular amyloid angiopathy (CAA), and/or tau pathology. The protein products within AD genetic risk loci were concentrated within cerebrovascular modules. The overlap between differentially abundant proteins in AD cerebrospinal fluid (CSF) and plasma with cerebrovascular network highlighted a significant increase of matrisome proteins, SMOC1 and SMOC2, in CSF, plasma, and brain., Discussion: These findings enhance our understanding of cerebrovascular deficits in AD, shedding light on potential biomarkers associated with CAA and vascular dysfunction in neurodegenerative diseases., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Determining whether the RNA isoforms from medically relevant genes have distinct functions could facilitate direct targeting of RNA isoforms for disease treatment. Here, as a step toward this goal for neurological diseases, we sequenced 12 postmortem, aged human frontal cortices (6 Alzheimer disease cases and 6 controls; 50% female) using one Oxford Nanopore PromethION flow cell per sample. We identified 1,917 medically relevant genes expressing multiple isoforms in the frontal cortex where 1,018 had multiple isoforms with different protein-coding sequences. Of these 1,018 genes, 57 are implicated in brain-related diseases including major depression, schizophrenia, Parkinson's disease and Alzheimer disease. Our study also uncovered 53 new RNA isoforms in medically relevant genes, including several where the new isoform was one of the most highly expressed for that gene. We also reported on five mitochondrially encoded, spliced RNA isoforms. We found 99 differentially expressed RNA isoforms between cases with Alzheimer disease and controls., (© 2024. The Author(s).)

Walking performance and cognitive function demonstrate strong associations in older adults, with both declining with advancing age. Walking requires the use of cognitive resources, particularly in complex environments like stepping over obstacles. A commonly implemented approach for measuring the cognitive control of walking is a dual-task walking assessment, in which walking is combined with a second task. However, dual-task assessments have shortcomings, including issues with scaling the task difficulty and controlling for task prioritization. Here we present a new assessment designed to be less susceptible to these shortcomings while still challenging cognitive control of walking: the Obstructed Vision Obstacle (OBVIO) task. During the task, participants hold a lightweight tray at waist level obstructing their view of upcoming foam blocks, which are intermittently spaced along a 10 m walkway. This forces the participants to use cognitive resources (e.g., attention and working memory) to remember the exact placement of upcoming obstacles to facilitate successful crossing. The results demonstrate that adding the obstructed vision board significantly slowed walking speed by an average of 0.26 m/s and increased the number of obstacle strikes by 8-fold in healthy older adults (n = 74). Additionally, OBVIO walking performance (a score based on both speed and number of obstacle strikes) significantly correlated with computer-based assessments of visuospatial working memory, attention, and verbal working memory. These results provide initial support that the OBVIO task is a feasible walking test that demands cognitive resources. This study lays the groundwork for using the OBVIO task in future assessment and intervention studies., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest., (Published by Elsevier Inc.)

Individuals with a spinal cord injury (SCI) have challenges using transportation. Autonomous shuttles (ASs), if accessible, may support their transportation needs. This study quantified the perceptions of AS for adults with and without SCI, before and after riding in the AS. We hypothesized that the perceptions of AS for individuals with SCI would improve, by the greatest magnitude, after riding in the AS. This mixed-method quasi-experimental design included 16 adults with SCI and 16 age-matched controls. While there were no differences between the groups, both groups reported having fewer perceived barriers to using AS after riding in the AS ( p = .025). After riding in the AS, both groups stated that the AS must be available, accessible, and affordable if they are to use AS. In conclusion, adults with SCI should experience AS if they are to accept and adopt this mode of transportation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Backward walking (BW) is an important gait adaptation and BW speed may be an important indicator of walking function and fall risk. However, the measurement characteristics of a standardized assessment of BW post-stroke have not been fully established., Objectives: To determine intra- and interrater reliability, concurrent validity and minimal detectable change (MDC) scores for the 3-Meter Backward Walk Test (3MBWT) post-stroke., Methods: Thirty-four individuals with subacute and 29 individuals with chronic stroke participated. Two trials of comfortable BW was measured over a total distance of 5-meters, while speed was calculated during the middle 3-meters of the walking distance. Intra and interrater reliability were determined by comparing the two trials from one rater and simultaneous assessment of two raters, respectively. Two additional trials were performed and BW speed was calculated using 3MBWT and an instrumented walkway to determine concurrent validity. Intraclass correlation coefficients (ICC) estimated reliability and validity. The MDC was calculated from the standard error of measurement., Results: Excellent ICC values were obtained for the 3MBWT in the subacute (interrater: ICC 2,1  = 0.99; intrarater: ICC 2,1  = 0.96; validity: ICC 2,1  = 0.96) and chronic (interrater: ICC 2,1  = 0.99; intrarater: ICC 2,1  = 0.94; validity: ICC 2,1  = 0.97) groups. The MDC was 0.07 m/s (subacute) and 0.11 m/s (chronic)., Conclusions: Establishment of the 3MBWT as a reliable and valid measure in assessing BW speed is an important addition to the assessment toolbox for rehabilitation post-stroke.

Stroke survivors frequently report increased perceived challenge of walking (PCW) in complex environments, restricting their daily ambulation. PCW is conventionally measured through subjective questionnaires or, more recently, through objective quantification of sympathetic nervous system activity during walking tasks. However, how these measurements of PCW reflect daily walking activity post-stroke is unknown. We aimed to compare the subjective and objective assessments of PCW in predicting home and community ambulation. In 29 participants post-stroke, we measured PCW subjectively with the Activities-specific Balance Confidence (ABC) Scale and objectively through electrodermal activity, quantified by change in skin conductance levels (SCL) and skin conductance responses (SCR) between outdoor-complex and indoor-steady-state walking. High-PCW participants were categorized into high-change SCL (ΔSCL ≥ 1.7 μs), high-change SCR (ΔSCR ≥ 0.2 μs) and low ABC (ABC < 72%) groups, while low-PCW participants were categorized into low-change SCL (ΔSCL < 1.7 μs), low-change SCR (ΔSCR < 0.2 μs) and high-ABC (ABC ≥ 72%) groups. Number and location of daily steps were quantified with accelerometry and Global Positioning System devices. Compared to low-change SCL group, the high-change SCL group took fewer steps in home and community (p = 0.04). Neither ABC nor SCR groups differed in home or community steps/day. Objective measurement of PCW via electrodermal sensing more accurately represents home and community ambulation compared to the subjective questionnaire., (© 2023. The Author(s).)

Studying proteomics data of the human brain could offer numerous insights into unraveling the signature of resilience to Alzheimer's disease. In our previous study with rigorous cohort selection criteria that excluded 4 common comorbidities, we harnessed multiple brain regions from 43 research participants with 12 of them displaying cognitive resilience to Alzheimer's disease. Based on the previous findings, this work focuses on 6 proteins out of the 33 differentially expressed proteins associated with resilience to Alzheimer's disease. These proteins are used to construct a decision tree classifier, enabling the differentiation of 3 groups: (i) healthy control, (ii) resilience to Alzheimer's disease, and (iii) Alzheimer's disease with dementia. Our analysis unveiled 2 important regional proteomic markers: Aβ peptides in the hippocampus and PA1B3 in the inferior parietal lobule. These findings underscore the potential of using distinct regional proteomic markers as signatures in characterizing the resilience to Alzheimer's disease., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Comparing brain structure across species and regions enables key functional insights. Leveraging publicly available data from a novel mass cytometry-based method, synaptometry by time of flight (SynTOF), we applied an unsupervised machine learning approach to conduct a comparative study of presynapse molecular abundance across three species and three brain regions. We used neural networks and their attractive properties to model complex relationships among high dimensional data to develop a unified, unsupervised framework for comparing the profile of more than 4.5 million single presynapses among normal human, macaque, and mouse samples. An extensive validation showed the feasibility of performing cross-species comparison using SynTOF profiling. Integrative analysis of the abundance of 20 presynaptic proteins revealed near-complete separation between primates and mice involving synaptic pruning, cellular energy, lipid metabolism, and neurotransmission. In addition, our analysis revealed a strong overlap between the presynaptic composition of human and macaque in the cerebral cortex and neostriatum. Our unique approach illuminates species- and region-specific variation in presynapse molecular composition., (© 2023. Springer Nature Limited.)

Assay for Transposase Accessible Chromatin by sequencing (ATAC-seq) accurately depicts the chromatin regulatory state and altered mechanisms guiding gene expression in disease. However, bulk sequencing entangles information from different cell types and obscures cellular heterogeneity. To address this, we developed Cellformer, a deep learning method that deconvolutes bulk ATAC-seq into cell type-specific expression across the whole genome. Cellformer enables cost-effective cell type-specific open chromatin profiling in large cohorts. Applied to 191 bulk samples from 3 brain regions, Cellformer identifies cell type-specific gene regulatory mechanisms involved in resilience to Alzheimer's disease, an uncommon group of cognitively healthy individuals that harbor a high pathological load of Alzheimer's disease. Cell type-resolved chromatin profiling unveils cell type-specific pathways and nominates potential epigenetic mediators underlying resilience that may illuminate therapeutic opportunities to limit the cognitive impact of the disease. Cellformer is freely available to facilitate future investigations using high-throughput bulk ATAC-seq data., (© 2023. Springer Nature Limited.)

Introduction: Post-mortem analysis provides definitive diagnoses of neurodegenerative diseases; however, only a few can be diagnosed during life., Methods: This study employed statistical tools and machine learning to predict 17 neuropathologic lesions from a cohort of 6518 individuals using 381 clinical features (Table S1). The multisite data allowed validation of the model's robustness by splitting train/test sets by clinical sites. A similar study was performed for predicting Alzheimer's disease (AD) neuropathologic change without specific comorbidities., Results: Prediction results show high performance for certain lesions that match or exceed that of research annotation. Neurodegenerative comorbidities in addition to AD neuropathologic change resulted in compounded, but disproportionate, effects across cognitive domains as the comorbidity number increased., Discussion: Certain clinical features could be strongly associated with multiple neurodegenerative diseases, others were lesion-specific, and some were divergent between lesions. Our approach could benefit clinical research, and genetic and biomarker research by enriching cohorts for desired lesions., (© 2023 the Alzheimer's Association.)

Rationale: Acute intermittent hypoxia (AIH) shows promise for enhancing motor recovery in chronic spinal cord injuries and neurodegenerative diseases. However, human trials of AIH have reported significant variability in individual responses., Objectives: Identify individual factors (eg, genetics, age, and sex) that determine response magnitude of healthy adults to an optimized AIH protocol, acute intermittent hypercapnic-hypoxia (AIHH)., Methods: In 17 healthy individuals (age = 27 ± 5 yr), associations between individual factors and changes in the magnitude of AIHH (15, 1-min O2 = 9.5%, CO2 = 5% episodes) induced changes in diaphragm motor-evoked potential (MEP) amplitude and inspiratory mouth occlusion pressures (P0.1) were evaluated. Single nucleotide polymorphisms (SNPs) in genes linked with mechanisms of AIH induced phrenic motor plasticity ( BDNF, HTR2A, TPH2, MAOA, NTRK2 ) and neuronal plasticity (apolipoprotein E, APOE ) were tested. Variations in AIHH induced plasticity with age and sex were also analyzed. Additional experiments in humanized (h) ApoE knock-in rats were performed to test causality., Results: AIHH-induced changes in diaphragm MEP amplitudes were lower in individuals heterozygous for APOE4 (i.e., APOE3 / 4 ) compared to individuals with other APOE genotypes ( P = 0.048) and the other tested SNPs. Males exhibited a greater diaphragm MEP enhancement versus females, regardless of age ( P = 0.004). Additionally, age was inversely related with change in P0.1 ( P = 0.007). In h ApoE4 knock-in rats, AIHH-induced phrenic motor plasticity was significantly lower than h ApoE3 controls ( P < 0.05)., Conclusions: APOE4 genotype, sex, and age are important biological determinants of AIHH-induced respiratory motor plasticity in healthy adults., Addition to Knowledge Base: AIH is a novel rehabilitation strategy to induce functional recovery of respiratory and non-respiratory motor systems in people with chronic spinal cord injury and/or neurodegenerative disease. Figure 5 Since most AIH trials report considerable inter-individual variability in AIH outcomes, we investigated factors that potentially undermine the response to an optimized AIH protocol, AIHH, in healthy humans. We demonstrate that genetics (particularly the lipid transporter, APOE ), age and sex are important biological determinants of AIHH-induced respiratory motor plasticity., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Physiological Society.)

Backward walking training has been reported to improve gait speed and balance post-stroke. However, it is not known if gains are achieved through recovery of the paretic limb or compensations from the nonparetic limb. The purpose of this study was to compare the influence of backward locomotor training (BLT) versus forward locomotor training (FLT) on gait speed and dynamic balance control, and to quantify the underlying mechanisms used to achieve any gains. Eighteen participants post chronic stroke were randomly assigned to receive 18 sessions of either FLT (n = 8) or BLT (n = 10). Pre- and post-intervention outcomes included gait speed (10-meter Walk Test) and forward propulsion (time integral of anterior-posterior ground-reaction-forces during late stance for each limb). Dynamic balance control was assessed using clinical (Functional Gait Assessment) and biomechanical (peak-to-peak range of whole-body angular-momentum in the frontal plane) measures. Balance confidence was assessed using the Activities-Specific Balance Confidence scale. While gait speed and balance confidence improved significantly within the BLT group, these improvements were associated with an increased nonparetic limb propulsion generation, suggesting use of compensatory mechanisms. Although there were no improvements in gait speed within the FLT group, paretic limb propulsion generation significantly improved post-FLT, suggesting recovery of the paretic limb. Neither training group improved in dynamic balance control, implying the need of balance specific training along with locomotor training to improve balance control post-stroke. Despite the within-group differences, there were no significant differences between the FLT and BLT groups in the achieved gains in any of the outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The immature central nervous system is recognized as having substantial neuroplastic capacity. In this study, we explored the hypothesis that rehabilitation can exploit that potential and elicit reciprocal walking in nonambulatory children with chronic, severe (i.e., lower extremity motor score < 10/50) spinal cord injuries (SCIs). Seven male subjects (3-12 years of age) who were at least 1-year post-SCI and incapable of discrete leg movements believed to be required for walking, enrolled in activity-based locomotor training (ABLT; clinicaltrials.gov NCT00488280). Six children completed the study. Following a minimum of 49 sessions of ABLT, three of the six children achieved walking with reverse rolling walkers. Stepping development, however, was not accompanied by improvement in discrete leg movements as underscored by the persistence of synergistic movements and little change in lower extremity motor scores. Interestingly, acoustic startle responses exhibited by the three responding children suggested preserved reticulospinal inputs to circuitry below the level of injury capable of mediating leg movements. On the other hand, no indication of corticospinal integrity was obtained with transcranial magnetic stimulation evoked responses in the same individuals. These findings suggest some children who are not predicted to improve motor and locomotor function may have a reserve of adaptive plasticity that can emerge in response to rehabilitative strategies such as ABLT. Further studies are warranted to determine whether a critical need exists to re-examine rehabilitation approaches for pediatric SCI with poor prognosis for any ambulatory recovery., (© 2023 Wiley Periodicals LLC.)

Resilience to Alzheimer's disease is an uncommon combination of high disease burden without dementia that offers valuable insights into limiting clinical impact. Here we assessed 43 research participants meeting stringent criteria, 11 healthy controls, 12 resilience to Alzheimer's disease and 20 Alzheimer's disease with dementia and analyzed matched isocortical regions, hippocampus, and caudate nucleus by mass spectrometry-based proteomics. Of 7115 differentially expressed soluble proteins, lower isocortical and hippocampal soluble Aβ levels is a significant feature of resilience when compared to healthy control and Alzheimer's disease dementia groups. Protein co-expression analysis reveals 181 densely-interacting proteins significantly associated with resilience that were enriched for actin filament-based processes, cellular detoxification, and wound healing in isocortex and hippocampus, further supported by four validation cohorts. Our results suggest that lowering soluble Aβ concentration may suppress severe cognitive impairment along the Alzheimer's disease continuum. The molecular basis of resilience likely holds important therapeutic insights., (© 2023. The Author(s).)

Background: Walking at fast speed is a gait training strategy post-stroke. It is unknown how faster-than-preferred pace impacts spatiotemporal gait characteristics in survivors with different functional abilities., Objective: To test the hypothesis that compared to high-functioning individuals, low-functioning individuals will be limited in modifying spatiotemporal gait parameters for walking at faster-than-preferred speed, and these limitations are associated with fear of falling., Methods: Forty-two adults, 17.6 ± 14.6 months post-stroke, traversed an instrumented walkway at preferred and fast speeds. Participants were categorized to a low-functioning group (LFG) (n = 20; <0.45 m/s) and high-functioning group (HFG) (n = 22; ≥0.45 m/s). Cadence, step length, stance time and spatiotemporal asymmetry measures were calculated. The Modified Falls-efficacy Scale examined fear of falling. Multivariate and correlational analysis tested hypotheses., Results: Increased speed from preferred to fast pace was significantly greater for HFG (0.27 ± 0.03 m/s) than LFG (0.10 ± 0.02 m/s) ( p ≤ 0.001 ). Cadence gain from preferred to fast pace did not differ between groups. However, HFG exhibited greater change in paretic (∆6.1 ± 1.37 cm; p < .001 ) and non-paretic step lengths (∆4.5 ± 1.37 cm; p = .003 ) than LFG. Spatiotemporal asymmetry did not change for either group. Fear of falling had moderately positive correlation with ∆paretic step length ( r = 0.43; p = .004 ) and ∆non-paretic step length ( r = 0.32; p = .035 )., Conclusions: While both low- and high-functioning individuals used a step-lengthening strategy to walk at faster-than-preferred speeds, the gain in step lengths was limited in low-functioning individuals and was partially explained by falls-efficacy.

Study Design: Feasibility study, consisting of random-order, cross-over study of a single intervention session, followed by a parallel-arm study of 16 sessions., Objectives: To investigate the feasibility of a novel combinatorial approach with simultaneous delivery of transcutaneous spinal direct current stimulation (tsDCS) and locomotor training (tsDCS + LT) after spinal cord injury, compared to sham stimulation and locomotor training (sham + LT), and examine preliminary effects on walking function., Setting: Clinical research center in the southeastern United States., Methods: Eight individuals with chronic incomplete spinal cord injury (ISCI) completed the two-part protocol. Feasibility was assessed based on safety (adverse responses), tolerability (pain, spasticity, skin integrity), and protocol achievement (session duration, intensity). Walking function was assessed with the 10 m and 6 min walk tests., Results: There were no major adverse responses. Minimal reports of skin irritation and musculoskeletal pain were consistent between groups. Average training peak heart rate as percent of maximum (mean(SD); tsDCS + LT: 66 (4)%, sham + LT: 69 (10)%) and Borg ratings of perceived exertion (tsDCS + LT: 17.5 (1.2), sham + LT: 14.4 (1.8)) indicate both groups trained at high intensities. Walking speed gains exceeded the minimal clinically important difference (MCID) in three of four who received tsDCS + LT (0.18 (0.29) m/s) and one of four in sham + LT (-0.05 (0.23) m/s). Gains in walking endurance exceeded the MCID in one of four in each group (tsDCS + LT: 36.4 (69.0) m, sham + LT: 4.9 (56.9) m)., Conclusions: Combinatorial tsDCS and locomotor training is safe and feasible for individuals with chronic ISCI, even those with considerable walking impairment. Study outcomes support the need to investigate the efficacy of this approach., (© 2022. The Author(s), under exclusive licence to International Spinal Cord Society.)

We report on the initial 17 (11 male:6 female) brain autopsies from across Europe and the United States in the Parkinson's Progression Markers Initiative (PPMI). Clinical diagnoses were Parkinson's disease (n = 15), multiple system atrophy (n = 1), and Dementia with Lewy bodies (n = 1); average age of death = 72 ± 8 yr. Cognitive assessment at last evaluation was 5 with normal cognition, 7 with mild cognitive impairment, and 5 with dementia. Genetic assessment showed 4 participants were heterozygous or homozygous for GBA N370S and 3 were heterozygous carriers for LRRK2 R1441G or G2019S; 1 was an APOE ε2 carrier and 5 were APOE ε4 carriers. Longitudinal DAT neuroimaging as well as CSF and plasma biomarker data are summarized. Neuropathologic examination confirmed all clinical diagnoses and showed the expected frequencies of common comorbidities; no evidence of chronic traumatic encephalopathy was observed. Thus, brain autopsy data can provide confirmation, clarification, and new insights into the PD progression observed during life. As it grows, the PPMI brain autopsy program will provide a deeply-annotated research resource to the community of investigators focused on developing biomarkers for PD progression., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Acute intermittent hypoxia (AIH) elicits long-term facilitation (LTF) of respiration. Although LTF is observed when CO 2 is elevated during AIH in awake humans, the influence of CO 2 on corticospinal respiratory motor plasticity is unknown. Thus, we tested the hypotheses that acute intermittent hypercapnic-hypoxia (AIHH): (1) enhances cortico-phrenic neurotransmission (reflecting volitional respiratory control); and (2) elicits ventilatory LTF (reflecting automatic respiratory control). Eighteen healthy adults completed four study visits. Day 1 consisted of anthropometry and pulmonary function testing. On Days 2, 3 and 4, in a balanced alternating sequence, participants received: AIHH, poikilocapnic AIH, and normocapnic-normoxia (Sham). Protocols consisted of 15, 60 s exposures with 90 s normoxic intervals. Transcranial (TMS) and cervical (CMS) magnetic stimulation were used to induce diaphragmatic motor-evoked potentials and compound muscle action potentials, respectively. Respiratory drive was assessed via mouth occlusion pressure (P 0.1 ), and minute ventilation measured at rest. Dependent variables were assessed at baseline and 30-60 min after exposures. Increases in TMS-evoked diaphragm potential amplitudes were observed following AIHH vs. Sham (+28 ± 41%, P = 0.003), but not after AIH. No changes were observed in CMS-evoked diaphragm potential amplitudes. Mouth occlusion pressure also increased after AIHH (+21 ± 34%, P = 0.033), but not after AIH. Ventilatory LTF was not observed after any treatment. We demonstrate that AIHH elicits central neural mechanisms of respiratory motor plasticity and increases resting respiratory drive in awake humans. These findings may have important implications for neurorehabilitation after spinal cord injury and other neuromuscular disorders compromising breathing. KEY POINTS: The occurrence of respiratory long-term facilitation following acute exposure to intermittent hypoxia is believed to be dependent upon CO 2 regulation - mechanisms governing the critical role of CO 2 have seldom been explored. We tested the hypothesis that acute intermittent hypercapnic-hypoxia (AIHH) enhances cortico-phrenic neurotransmission in awake healthy humans. The amplitude of diaphragmatic motor-evoked potentials induced by transcranial magnetic stimulation was increased after AIHH, but not the amplitude of compound muscle action potentials evoked by cervical magnetic stimulation. Mouth occlusion pressure (P 0.1 , an indicator of neural respiratory drive) was also increased after AIHH, but not tidal volume or minute ventilation. Thus, moderate AIHH elicits central neural mechanisms of respiratory motor plasticity, without measurable ventilatory long-term facilitation in awake humans., (© 2022 The Authors. The Journal of Physiology © 2022 The Physiological Society.)

Background: This study evaluated the incidence of de novo bone metastasis across all primary cancer sites and their impact on survival by primary cancer site, age, race, and sex., Questions/purposes: Our objectives were (I) characterize the epidemiology of de novo bone metastasis with respect to patient demographics, (II) characterize the incidence by primary site, age, and sex (2010-2015), and (III) compare survival of de novo metastatic cancer patients with and without bone metastasis., Methods: This is a retrospective, population-based study using nationally representative data from the Surveillance, Epidemiology, and End Results program, 2010-2015. Incidence rates by year of diagnosis, annual percentage changes, Kaplan-Meier, univariate and multiple Cox regression models are included in the analysis., Results: Of patients with cancer in the SEER database, 5.1% were diagnosed with metastasis to bone, equaling ~18.8 per 100,000 bone metastasis diagnoses in the US per year (2010-2015). For adults >25, lung cancer is the most common primary site (2015 rate: 8.7 per 100,000) with de novo bone metastases, then prostate and breast primaries (2015 rates: 3.19 and 2.38 per 100,000, respectively). For patients <20 years old, endocrine cancers and soft tissue sarcomas are the most common primaries. Incidence is increasing for prostate (Annual Percentage Change (APC) = 4.6%, P < 0.001) and stomach (APC = 5.0%, P = 0.001) cancers. The presence of de novo bone metastasis was associated with a limited reduction in overall survival (HR = 1.02, 95%, CI = [1.01-1.03], p < 0.001) when compared to patients with other non-bone metastases., Conclusion: The presence of bone metastasis versus metastasis to other sites has disease site-specific impact on survival. The incidence of de novo bone metastasis varies by age, sex, and primary disease site., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS)., Objective: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion., Methods: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUC τ ) and maximum plasma concentration ( C max ) for Weeks 8-12. B-cell depletion and safety/tolerability were assessed., Results: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUC τ , 487.7 vs 474.1 h × µg/mL (ratio 1.03); C max , 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated., Conclusion: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion.

Study Design: Observational, analytical cohort study., Objectives: After incomplete spinal cord injury (iSCI), propriospinal pathways may remain intact enabling coupling between respiration and locomotion. This locomotor-respiratory coupling (LRC) may enable coordination between these two important behaviors and have implications for rehabilitation after iSCI. However, coordination between these behaviors is not well understood and it is unknown if iSCI disrupts LRC. The objective of this study was to compare LRC in ambulatory adults with iSCI to able-bodied controls., Setting: Rehabilitation Research Center, Jacksonville, Florida, United States of America., Methods: Adults with iSCI (4 males, 1 female) and able-bodied controls (2 males, 3 females) walked at their fastest comfortable speed for 6 min over ground, and on a treadmill with bodyweight support (10-20%) and as-needed assistance at a standardized fast speed (controls) or their fastest speed (iSCI) for 6 min. LRC was quantified as the percent of breaths that were coupled with steps at a consistent ratio during the last 4 min of each walking condition., Results: Over ground, participants with iSCI demonstrated significantly more LRC than able-bodied controls (72.4 ± 6.4% vs. 59.1% ± 7.5, p = 0.016). During treadmill walking, LRC did not differ between groups (iSCI 67.5 ± 15.8% vs. controls 66.3 ± 4.0%, p > 0.05)., Conclusions: Adults with iSCI demonstrated similar or greater LRC compared to able-bodied controls. This suggests that pathways subserving coordination between these behaviors remain intact in this group of individuals who walk independently after iSCI., (© 2022. The Author(s), under exclusive licence to International Spinal Cord Society.)