Application of virtual reality for peritoneal dialysis exchange learning in patients with end-stage renal disease and cognitive impairment.

Cognitive impairment is not uncommon in patients with end-stage renal disease and can make it more difficult for these patients to carry out peritoneal dialysis (PD) on their own. Their attempts to do so may result in adverse consequences such as peritonitis. PD exchange is a complex procedure demanding knowledge and skill which requires close supervision and guidance by a renal nurse specialist. In this study, a non-immersive virtual reality (VR) training program using a Leap motion hand tracking device was developed to facilitate patients' understanding and learning of the PD exchange procedure before attempting real task practice. This study was a two-center single-blinded randomized controlled trial on 23 incident PD patients. Patients in the experimental group received 8 sessions of VR training, while patients in the control were provided with printed educational materials. The results showed that there were significant differences between the two groups in performance of the overall PD exchange sequence, especially on the crucial steps. VR had a patient satisfaction rate of 89%, and all patients preferred to have the VR aid incorporated in PD training. Our findings conclude VR can be a useful aid in the training and reinforcement of PD exchange procedures, with distinct merits of being free from restrictions of time, space, and manpower.

Design principles of regulatory networks: searching for the molecular algorithms of the cell.

A challenge in biology is to understand how complex molecular networks in the cell execute sophisticated regulatory functions. Here we explore the idea that there are common and general principles that link network structures to biological functions, principles that constrain the design solutions that evolution can converge upon for accomplishing a given cellular task. We describe approaches for classifying networks based on abstract architectures and functions, rather than on the specific molecular components of the networks. For any common regulatory task, can we define the space of all possible molecular solutions? Such inverse approaches might ultimately allow the assembly of a design table of core molecular algorithms that could serve as a guide for building synthetic networks and modulating disease networks.

Five-year PFS from the AETHERA trial of brentuximab vedotin for Hodgkin lymphoma at high risk of progression or relapse.

The phase 3 AETHERA trial established brentuximab vedotin (BV) as a consolidative treatment option for adult patients with classical Hodgkin lymphoma (cHL) at high risk of relapse or progression after autologous hematopoietic stem-cell transplantation (auto-HSCT). Results showed that BV significantly improved progression-free survival (PFS) vs placebo plus best supportive care alone. At 5-year follow-up, BV continued to provide patients with sustained PFS benefit; 5-year PFS was 59% (95% confidence interval [CI], 51-66) with BV vs 41% (95% CI, 33-49) with placebo (hazard ratio [HR], 0.521; 95% CI, 0.379-0.717). Similarly, patients with ≥2 risk factors in the BV arm experienced significantly higher PFS at 5 years than patients in the placebo arm (HR, 0.424; 95% CI, 0.302-0.596). Upfront consolidation with BV significantly delayed time to second subsequent therapy, an indicator of ongoing disease control, vs placebo. Peripheral neuropathy, the most common adverse event in patients receiving BV, continued to improve and/or resolve in 90% of patients. In summary, consolidation with BV in adult patients with cHL at high risk of relapse or progression after auto-HSCT confers a sustained PFS benefit and is safe and well tolerated. Physicians should consider each patient's HL risk factor profile when making treatment decisions. This trial was registered at www.clinicaltrials.gov as #NCT01100502.

Do male engagement and couples' communication influence maternal health care-seeking? Findings from a household survey in Mozambique.

BACKGROUND: This study explored effects of couples' communication and male participation in birth preparedness and complication readiness (BPCR) on delivery in a health facility ("institutional delivery"). A cross-sectional, baseline household survey was conducted in November 2016 prior to an integrated maternal and child health project in Nampula and Sofala Provinces in Mozambique. METHODS: The study used the Knowledge, Practices and Coverage survey tool, a condensed version of the Demographic and Health Survey and other tools. The sample included 1422 women. Multivariable logit regression models tested the association of institutional delivery with couples' communication and four elements of BPCR both with and without male partners: 1) saving money, 2) arranging transport, 3) choosing a birth companion, and 4) choosing a delivery site; controlling for partners' attendance in antenatal care and social and demographic determinants (education, wealth, urban/rural location, and province). RESULTS: The odds that women would deliver in a health facility were 46% greater (adjusted odds ratio (aOR) = 1.46, 95% confidence interval (CI) = 1.02-2.10, p = 0.04) amongst women who discussed family planning with their partners than those who did not. Approximately half of this effect was mediated through BPCR. When a woman arranged transport on her own, there was no significant increase in institutional delivery, but with partner involvement, there was a larger, significant association (aOR = 4.31, 2.64-7.02). Similarly, when a woman chose a delivery site on her own, there was no significant association with institutional delivery (aOR 1.52,0.81-2.83), but with her partner, there was a larger and significant association (aOR 1.98, 1.16-3.36). Neither saving money nor choosing a birth companion showed a significant association with institutional delivery-with or without partner involvement. The odds of delivering in a facility were 28% less amongst poor women whose partners did not participate in BPCR than wealthy women, but when partners helped choose a place of delivery and arrange transport, this gap was nearly eliminated. CONCLUSIONS: Our findings add to growing global evidence that men play an important role in improving maternal and newborn health, particularly through BPCR, and that couples' communication is a key approach for promoting high-impact health behaviors.

Speaking Up For Science.

Communicating science and being an advocate for public support of research are critical roles for scientists. However, despite having the most relevant expertise, many of us do not get involved in matters bridging science and policy. Here I discuss the importance of science advocacy by researchers, and present strategies for communicating the relevance of your work to the public and elected officials, including the crafting of a two-minute pitch - a valuable skill for all scientists.

MRI does not predict pathologic complete response after neoadjuvant chemotherapy for breast cancer.

BACKGROUND: This study assessed whether magnetic resonance imaging (MRI) could accurately predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for patients receiving standardized treatment, pre- and post-NAC MRI on the same instrumentation using a consistent imaging protocol, interpreted by a single breast fellowship-trained radiologist. METHODS: A single-institution retrospective analysis was performed including clinical, radiographic, and pathologic parameters for all patients with breast cancer treated with NAC from 2015 to 2018. Radiographic complete response (rCR) was defined as absence of suspicious MRI findings in the ipsilateral breast or lymph nodes. pCR was defined as the absence of invasive cancer or ductal carcinoma in-situ in breast or lymph nodes after operation (ypT0N0M0). RESULTS: Data for 102 consecutive patients demonstrated that 44 (43.1%) had rCR and 41 (40.1%) had pCR. pCR occurred in 12 (25.0%) of 48 estrogen receptor positive (ER+) patients, 29 (53.7%) of 54 ER- patients, and 25 (52.1%) of 48 human epidermal growth factor receptor 2 positive patients. The positive predictive value for MRI after NAC was 84.5% and the negative predictive value was 72.7%. The accuracy rate for MRI was 78.6%. Of the 44 patients with rCR, 12 (27.3%) had residual cancer on the pathologic specimen after surgical excision. CONCLUSION: rCR is not accurate enough to serve as a surrogate marker for pCR on MRI after NAC.

Sulfurization of Dissolved Organic Matter Increases Hg-Sulfide-Dissolved Organic Matter Bioavailability to a Hg-Methylating Bacterium.

Reactions of dissolved organic matter (DOM) with aqueous sulfide (termed sulfurization) in anoxic environments can substantially increase DOM's reduced sulfur functional group content. Sulfurization may affect DOM-trace metal interactions, including complexation and metal-containing particle precipitation, aggregation, and dissolution. Using a diverse suite of DOM samples, we found that susceptibility to additional sulfur incorporation via reaction with aqueous sulfide increased with increasing DOM aromatic-, carbonyl-, and carboxyl-C content. The role of DOM sulfurization in enhancing Hg bioavailability for microbial methylation was evaluated under conditions typical of Hg methylation environments (µM sulfide concentrations and low Hg-to-DOM molar ratios). Under the conditions of predicted metacinnabar supersaturation, microbial Hg methylation increased with increasing DOM sulfurization, likely reflecting either effective inhibition of metacinnabar growth and aggregation or the formation of Hg(II)-DOM thiol complexes with high bioavailability. Remarkably, Hg methylation efficiencies with the most sulfurized DOM samples were similar (>85% of total Hg methylated) to that observed in the presence of l-cysteine, a ligand facilitating rapid Hg(II) biouptake and methylation. This suggests that complexes of Hg(II) with DOM thiols have similar bioavailability to Hg(II) complexes with low-molecular-weight thiols. Overall, our results are a demonstration of the importance of DOM sulfurization to trace metal and metalloid (especially mercury) fate in the environment. DOM sulfurization likely represents another link between anthropogenic sulfate enrichment and MeHg production in the environment.

Exceptional aggressiveness of cerebral cavernous malformation disease associated with PDCD10 mutations.

PURPOSE: The phenotypic manifestations of cerebral cavernous malformation disease caused by rare PDCD10 mutations have not been systematically examined, and a mechanistic link to Rho kinase-mediated hyperpermeability, a potential therapeutic target, has not been established. METHODS: We analyzed PDCD10 small interfering RNA-treated endothelial cells for stress fibers, Rho kinase activity, and permeability. Rho kinase activity was assessed in cerebral cavernous malformation lesions. Brain permeability and cerebral cavernous malformation lesion burden were quantified, and clinical manifestations were assessed in prospectively enrolled subjects with PDCD10 mutations. RESULTS: We determined that PDCD10 protein suppresses endothelial stress fibers, Rho kinase activity, and permeability in vitro. Pdcd10 heterozygous mice have greater lesion burden than other Ccm genotypes. We demonstrated robust Rho kinase activity in murine and human cerebral cavernous malformation vasculature and increased brain vascular permeability in humans with PDCD10 mutation. Clinical phenotype is exceptionally aggressive compared with the more common KRIT1 and CCM2 familial and sporadic cerebral cavernous malformation, with greater lesion burden and more frequent hemorrhages earlier in life. We first report other phenotypic features, including scoliosis, cognitive disability, and skin lesions, unrelated to lesion burden or bleeding. CONCLUSION: These findings define a unique cerebral cavernous malformation disease with exceptional aggressiveness, and they inform preclinical therapeutic testing, clinical counseling, and the design of trials.Genet Med 17 3, 188-196.

Discovery of consensus gene signature and intermodular connectivity defining self-renewal of human embryonic stem cells.

Molecular markers defining self-renewing pluripotent embryonic stem cells (ESCs) have been identified by relative comparisons between undifferentiated and differentiated cells. Most of analysis has been done under a specific differentiation condition that may present significantly different molecular changes over others. Therefore, it is currently unclear if there are true consensus markers defining undifferentiated human ESCs (hESCs). To identify a set of key genes consistently altered during differentiation of hESCs regardless of differentiation conditions, we have performed microarray analysis on undifferentiated hESCs (H1 and H9) and differentiated EBs and validated our results using publicly available expression array datasets. We constructed consensus modules by Weighted Gene Coexpression Network Analysis and discovered novel markers that are consistently present in undifferentiated hESCs under various differentiation conditions. We have validated top markers (downregulated: LCK, KLKB1, and SLC7A3; upregulated: RhoJ, Zeb2, and Adam12) upon differentiation. Functional validation analysis of LCK in self-renewal of hESCs using LCK inhibitor or gene silencing with siLCK resulted in a loss of undifferentiation characteristics-morphological change, reduced alkaline phosphatase activity, and pluripotency gene expression, demonstrating a potential functional role of LCK in self-renewal of hESCs. We have designated hESC markers to interactive networks in the genome, identifying possible interacting partners and showing how new markers relate to each other. Furthermore, comparison of these datasets with available datasets from induced pluripotent stem cells (iPSCs) revealed that the level of these newly identified markers was correlated to the establishment of iPSCs, which may imply a potential role of these markers in gaining of cellular potency.

Subpontic osseous hyperplasia: a case series and literature review.

A subpontic osseous hyperplasia (SOH) is a slow-growing, non-neoplastic bone growth that uniquely affects mandibular posterior edentulous ridges underneath pontics of fixed partial dentures. An SOH can result in significant periodontal and restorative complications, however, it is usually corrected by surgical excision. This report presents a series of SOH cases, illustrates SOH management approaches, and reviews the literature on SOH clinical presentations.

Health Professional vs Layperson Values and Preferences on Scarce Resource Allocation.

Importance: COVID-19 prompted rapid development of scarce resource allocation (SRA) policies to be implemented if demand eclipsed health systems' ability to provide critical care. While SRA policies follow general ethical frameworks, understanding priorities of those affected by policies and/or tasked with implementing them is critical. Objective: To evaluate whether community members and health care profesionals (HCP) agree with SRA protocols at the University of California (UC). Design, Setting, and Participants: This survey study used social media and community-partnered engagement to recruit participants to a web-based survey open to all participants aged older than 18 years who wished to enroll. This study was fielded between May and September 2020 and queried participants' values and preferences on draft SRA policy tenets. Participants were also encouraged to forward the survey to their networks for snowball sampling. Data were analyzed from July 2020 to January 2024. Main Outcomes and Measures: Survey items assessed values and preferences, graded on Likert scales. Agreement was tabulated as difference in Likert points between expressed opinion and policy tenets. Descriptive statistics were tested for significance by HCP status. Free text responses were analyzed using applied rapid qualitative analysis. Results: A total of 1545 participants aged older than 18 years (mean [SD] age 49 [16] years; 1149 female participants [74%], 478 health care practitioners [30%]) provided data on SRA values and preferences. Agreement with UC SRA policy as drafted was moderately high among respondents, ranging from 67% to 83% across domains. Higher agreement with the interim policy was observed for laypersons across all domains except health-related factors. HCPs agreed more strongly on average that resources should not be allocated to those less likely to survive (HCP mean, 3.70; 95% CI, 3.16-3.59; vs layperson mean, 3.38; 95% CI, 3.17-3.59; P = .002), and were more in favor of reallocating life support from patients less likely to those more likely to survive (HCP mean, 6.41; 95% CI, 6.15-6.67; vs layperson mean, 5.40; 95% CI, 5.23-5.58; P < .001). Transparency and trust building themes were common in free text responses and highly rated on scaled items. Conclusions and Relevance: This survey of SRA policy values found moderate agreement with fundamental principles of such policies. Engagement with communities affected by SRA policy should continue in iterative refinement in preparation for future crises.

High-Throughput Automatic Laser Printing Strategy toward Cost-effective Portable Integrated Urea Tele-Monitoring System.

A portable sweat urea sensing system is a promising solution to satisfy the booming requirement of kidney function tele-monitoring. However, the complicated manufacturing route and the cumbersome electrochemical testing system still need to be improved to develop the urea point-of-care testing (POCT) and tele-monitoring devices. Here, a universal technical route based on a high-throughput automatic laser printing strategy for fabricating the portable integrated urea monitoring system is proposed. This integrated system includes a high-performance laser-printed urea sensing electrode, a planar three-electrode system, and a self-developed wireless mini-electrochemical workstation. A precursor donor layer is activated by laser scribing and in situ transferred into functional nanoparticles for the drop-on-demand printing of the urea sensing electrode. The obtained electrodes show high sensitivity, low detection limit, fast response time, high selectivity, good average recovery, and long-term stability for urea sensing. Additionally, a laser-induced graphene circuit-based miniature planar three-electrode system and a wireless mini-electrochemical workstation are designed for sensing data collection and transmitting, achieving real-time urea POCT and tele-monitoring. This scalable method provides a universal solution for high-throughput and ultra-fast fabrication of urea-sensing electrodes. The portable integrated urea monitoring system is a competitive option to achieve cost-effective POCT and tele-monitoring for kidney function.

In situ Electrical Impedance Tomography for Visualizing Water Transportation in Hygroscopic Aerogels.

The global water crisis demands immediate attention, and atmospheric water harvesting (AWH) provides a viable alternative. However, studying the real-time subtle relationship between water absorption, diffusion, and internal structure for hygroscopic materials is challenging. Herein, a dynamic visualization technique is proposed that utilizes an in situ electrical impedance tomography (EIT) system and a precise reconstruction algorithm to achieve real-time monitoring of the water sorption process within aerogels from an internal microstructural perspective. These results can be inferred that composites' pore sizes affecting the kinetics of their moisture absorption. In addition, the diffusion path of moisture absorption and the distribution of stored moisture inside aerogels exhibit intrinsic self-selective behavior, where the fiber skeleton of the aerogel plays a crucial role. In summary, this work proposes a generic EIT-based technique for the in situ and dynamic monitoring of the hygroscopic process, pointing to an entirely new approach regarding research on AWH materials.

Multifunctional laser-induced graphene circuits and laser-printed nanomaterials toward non-invasive human kidney function monitoring.

Faced with the increasing prevalence of chronic kidney disease (CKD), portable monitoring of CKD-related biomarkers such as potassium ion (K+), creatinine (Cre), and lactic acid (Lac) levels in sweat has shown tremendous potential for early diagnosis. However, a rapidly manufacturable portable device integrating multiple CKD-related biomarker sensors for ease of sweat testing use has yet to be reported. Here, a portable electrochemical sensor integrated with multifunctional laser-induced graphene (LIG) circuits and laser-printed nanomaterials based working electrodes fabricated by fully automatic laser manufacturing is proposed for non-invasive human kidney function monitoring. The sensor comprises a two-electrode LIG circuit for K+ sensing, a three-electrode LIG circuit with a Kelvin compensating connection for Cre and Lac sensing, and a printed circuit board based portable electrochemical workstation. The working electrodes containing Cu and Cu2O nanoparticles fabricated by two-step laser printing show good sensitivity and selectivity toward Cre and Lac sensing. The sensor circuits are fabricated by generating a hydrophilic-hydrophobic interface on a patterned LIG through laser. This sensor recruited rapid laser manufacturing and integrated with multifunctional LIG circuits and laser-printed nanomaterials based working electrodes, which is a potential kidney function monitoring solution for healthy people and kidney disease patients.

Heterogeneous CuxO Nano-Skeletons from Waste Electronics for Enhanced Glucose Detection.

Electronic waste (e-waste) and diabetes are global challenges to modern societies. However, solving these two challenges together has been challenging until now. Herein, we propose a laser-induced transfer method to fabricate portable glucose sensors by recycling copper from e-waste. We bring up a laser-induced full-automatic fabrication method for synthesizing continuous heterogeneous CuxO (h-CuxO) nano-skeletons electrode for glucose sensing, offering rapid (< 1 min), clean, air-compatible, and continuous fabrication, applicable to a wide range of Cu-containing substrates. Leveraging this approach, h-CuxO nano-skeletons, with an inner core predominantly composed of Cu2O with lower oxygen content, juxtaposed with an outer layer rich in amorphous CuxO (a-CuxO) with higher oxygen content, are derived from discarded printed circuit boards. When employed in glucose detection, the h-CuxO nano-skeletons undergo a structural evolution process, transitioning into rigid Cu2O@CuO nano-skeletons prompted by electrochemical activation. This transformation yields exceptional glucose-sensing performance (sensitivity: 9.893 mA mM-1 cm-2; detection limit: 0.34 µM), outperforming most previously reported glucose sensors. Density functional theory analysis elucidates that the heterogeneous structure facilitates gluconolactone desorption. This glucose detection device has also been downsized to optimize its scalability and portability for convenient integration into people's everyday lives.

Serum metabolomics reveals lipid metabolism variation between coronary artery disease and congestive heart failure: a pilot study.

The aim of this pilot study is to find discriminating signals from the patient's congestive heart failure (HF) caused by coronary artery disease (CAD) through a non-target metabolomics method and test their usefulness in progress of human HF diseases. Multivariate data analysis was used to identify the discriminating signals. Interestingly, 12 metabolites contributing to the complete separation of HF from matched CAD were identified. Metabolic pathways including free fatty acids, sphingolipids and amino acid derivatives were found to be disturbed in HF patients compared with CAD patients. Lipid molecules associated with energy metabolism and signaling pathways may play key roles in the development of failing heart.

Laser-Induced Transfer of Functional Materials.

Patterning is crucial for the large-scale application of functional materials. Laser-induced transfer is an emerging patterning method for additively depositing functional materials to the target acceptor. With the rapid development of laser technologies, this laser printing method emerges as a versatile method to deposit functional materials in either liquid or solid format. The emerging applications such as solar interfacial evaporation, solar cells, light-emitting diodes, sensors, high-output synthesis, and other fields are rising fields benefiting from laser-induced transfer. Following a brief introduction to the principles of laser-induced transfer, this review will comprehensively deliberate this novel additive manufacturing method, including preparing the donor layer and the applications, advantages, and limitations of this technique. Finally, perspectives for handling current and future functional materials using laser-induced transfer will also be discussed. Non-experts in laser technologies can also gain insights into this prevailing laser-induced transfer process, which may inspire their future research.

"July effect": impact of the academic year-end changeover on patient outcomes: a systematic review.

BACKGROUND: It is commonly believed that the quality of health care decreases during trainee changeovers at the end of the academic year. PURPOSE: To systematically review studies describing the effects of trainee changeover on patient outcomes. DATA SOURCES: Electronic literature search of PubMed, Educational Research Information Center (ERIC), EMBASE, and the Cochrane Library for English-language studies published between 1989 and July 2010. STUDY SELECTION: Title and abstract review followed by full-text review to identify studies that assessed the effect of the changeover on patient outcomes and that used a control group or period as a comparator. DATA EXTRACTION: Using a standardized form, 2 authors independently abstracted data on outcomes, study setting and design, and statistical methods. Differences between reviewers were reconciled by consensus. Studies were then categorized according to methodological quality, sample size, and outcomes reported. DATA SYNTHESIS: Of the 39 included studies, 27 (69%) reported mortality, 19 (49%) reported efficiency (length of stay, duration of procedure, hospital charges), 23 (59%) reported morbidity, and 6 (15%) reported medical error outcomes; all studies focused on inpatient settings. Most studies were conducted in the United States. Thirteen (33%) were of higher quality. Studies with higher-quality designs and larger sample sizes more often showed increased mortality and decreased efficiency at time of changeover. Studies examining morbidity and medical error outcomes were of lower quality and produced inconsistent results. LIMITATIONS: The review was limited to English-language reports. No study focused on the effect of changeovers in ambulatory care settings. The definition of changeover, resident role in patient care, and supervision structure varied considerably among studies. Most studies did not control for time trends or level of supervision or use methods appropriate for hierarchical data. CONCLUSION: Mortality increases and efficiency decreases in hospitals because of year-end changeovers, although heterogeneity in the existing literature does not permit firm conclusions about the degree of risk posed, how changeover affects morbidity and rates of medical errors, or whether particular models are more or less problematic. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Introducing Long-Acting Contraceptive Removal Indicators in a Pilot Study in Mozambique: Dynamics of Discontinuation and Implications for Quality of Care.

INTRODUCTION: The recent increase in the use of long-acting reversible contraceptives (LARCs) will result in an equal increase in the need for removals. Few countries monitor the number of LARC removals and even fewer track reasons for removal, discontinuation, and method switching. We conducted a mixed-method study to pilot the introduction of 5 LARC removal indicators in Mozambique: (1) reason for seeking removal, (2) duration of use, (3) removal outcome, (4) reason for referral, and (5) family planning (FP) outcome. We assessed providers' perceptions about the feasibility and utility of tracking these indicators and reviewed the findings to ascertain the quality-of-care concerns. METHODS: We used a purposive, multistage sampling technique to select 19 intervention facilities in Nampula and Sofala provinces. Over 6 months, we abstracted data on the 5 indicators from an FP register addendum to determine when and why clients seek LARC removals and identify service quality issues that need to be addressed in the FP program. We used a supportive supervision checklist to assess the time taken to record data on the indicators and perceived benefits and challenges encountered by providers during record keeping. RESULTS: Of the 795 clients who sought a LARC removal, 112 women (14.1%) opted not to have the removal after counseling. The most frequently reported reasons for seeking a removal were: the method was on-schedule for removal or past its expiration date (29.5%), complaints of side effects (25.8%), and desire to be pregnant (22.9%). Health care providers reported no major challenges in recording information in the addendum. Reasons for and timing of removal pointed to the need for strengthening FP counseling. CONCLUSION: Collecting, synthesizing, and interpreting data from the LARC removal indicators was feasible and provided valuable insights to improve the quality of care to enhance clients' reproductive health care and contraceptive choices.

Robotic assistance that encourages the generation of stepping rather than fully assisting movements is best for learning to step in spinally contused rats.

Robotic devices have been developed to assist body weight-supported treadmill training (BWSTT) in individuals with spinal cord injuries (SCIs) and stroke. Recent findings have raised questions about the effectiveness of robotic training that fully assisted (FA) stepping movements. The purpose of this study was to examine whether assist-as-needed robotic (AAN) training was better than FA movements in rats with incomplete SCI. Electromyography (EMG) electrodes were implanted in the tibialis anterior and medial gastrocnemius hindlimb muscles of 14 adult rats. Afterward, the rats received a severe midthoracic spinal cord contusion and began daily weight-supported treadmill training 1 wk later using a rodent robotic system. During training, assistive forces were applied to the ankle when it strayed from a desired stepping trajectory. The amount of force was proportional to the magnitude of the movement error, and this was multiplied by either a high or low scale factor to implement the FA (n = 7) or AAN algorithms (n = 7), respectively. Thus FA training drove the ankle along the desired trajectory, whereas greater variety in ankle movements occurred during AAN training. After 4 wk of training, locomotor recovery was greater in the AAN group, as demonstrated by the ability to generate steps without assistance, more normal-like kinematic characteristics, and greater EMG activity. The findings suggested that flexible robotic assistance facilitated learning to step after a SCI. These findings support the rationale for the use of AAN robotic training algorithms in human robotic-assisted BWSTT.