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Drawing from fieldwork I conducted in Brussels with a group of drag kings in which I experience myself to perform a male character, and from my practice of dance and performance, I will focus my analysis on what I call “losing the self”. By “losing the self”, I mean a moment in which social actors, in the framework of a gendered and embodied transformational activity, experience to come out from the self and to welcome into one’s own body a desired self, and to becoming something/someone new. The analysis of this moment I experienced in the field, in which the transition from observer to participant status took place, and in which I experienced the transition from an assigned at birth masculinity to a king masculinity, allows me to highlight some central points for gender studies and performance studies, in particular, and for the social sciences, in general: How to think of transformational processes through a multidimensional perspective (i.e. verbal, tactile, visual, material) taking into account its public, reflexive, multimodal and indexical dimensions? Finally, how can we rethink the boundaries between observation and participation, art and life, and to think of science through the lens of experience and becoming?

Reducing the precious metal content of water oxidation catalysts for proton-exchange-membrane water electrolyzers remains a critical barrier to their large-scale deployment. Herein, we present an engineered architecture for supported iridium catalysts, which enables decreased precious metal content and improved activity and conductivity. The improvement in performance at lower precious metal loading is realized by the deposition of a conformal layer of platinum nanoparticles on titanium dioxide (TiO2) using a facile photoreduction method to prepare conductive layer coated supports (CCSs). Platinum nanoparticles are homogeneously dispersed on TiO2, and the conductivity of the subsequent catalysts with 39 wt % precious group metal loadings is significantly higher than the commercial 75 wt % loaded IrO2-TiO2 catalysts. The conformal conductive layer also maintains an enhanced conductivity and electrochemical activity upon thermal annealing when compared to catalysts without the conductive layer and nonconformal heterogeneous conductive layer. The iridium mass activity from half-cell studies shows a 141% improvement for CCS supported catalysts at 42% lower loadings compared to the commercial catalysts. The conductive layer also improves the single cell electrolyzer performance at a similar catalyst loading in comparison to a commercial state-of-the-art catalyst. We correlate the physical properties of the engineered catalysts with their electrochemical performance in electrolyzers to understand structure-activity relationships, and we anticipate further performance improvements upon synthesis and materials optimizations.

We report, to our knowledge for the first time, a combined experimental and density functional theory (DFT) investigation into the activity and stability of cobalt, molybdenum, and copper arsenides as catalysts for the hydrogen evolution reaction (HER). We find CoAs and MoAs to be the most active arsenide materials. We discuss the trends between calculated surface vacancy formation energies and catalyst stability. Using a simple thermodynamic model of HER activity, we find consistent trends between hydrogen binding free energy and the experimentally observed activity.

Background: Vγ9Vδ2 T-cells are antitumor immune effector cells that can detect metabolic dysregulation in cancer cells through phosphoantigen-induced conformational changes in the butyrophilin (BTN) 2A1/3A1 complex. In order to clinically exploit the anticancer properties of Vγ9Vδ2 T-cells, various approaches have been studied including phosphoantigen stimulation, agonistic BTN3A-specific antibodies, adoptive transfer of expanded Vγ9Vδ2 T-cells, and more recently bispecific antibodies. While Vγ9Vδ2 T-cells constitute a sizeable population, typically making up ~1-10% of the total T cell population, lower numbers have been observed with increasing age and in the context of disease., Methods: We evaluated whether bivalent single domain antibodies (VHHs) that link Vδ2-TCR specific VHHs with different affinities could support Vγ9Vδ2 T-cell expansion and could be incorporated in a bispecific engager format when additionally linked to a tumor antigen specific VHH., Results: Bivalent VHHs that link a high and low affinity Vδ2-TCR specific VHH can support Vγ9Vδ2 T-cell expansion. The majority of Vγ9Vδ2 T-cells that expanded following exposure to these bivalent VHHs had an effector or central memory phenotype and expressed relatively low levels of PD-1. Bispecific engagers that incorporated the bivalent Vδ2-TCR specific VHH as well as a tumor antigen specific VHH triggered antitumor effector functions and supported expansion of Vγ9Vδ2 T-cells in vitro and in an in vivo model in NOG-hIL-15 mice., Conclusion: By enhancing the number of Vγ9Vδ2 T-cells available to exert antitumor effector functions, these novel Vδ2-bivalent bispecific T cell engagers may promote the overall efficacy of bispecific Vγ9Vδ2 T-cell engagement, particularly in patients with relatively low levels of Vγ9Vδ2 T-cells., Competing Interests: NV. TG and HV own LAVA Therapeutics NV shares. DH, PY, VI-G, PH and HV are/were employed by LAVA Therapeutics NV. TG is scientific advisor to LAVA Therapeutics NV. The authors declare that this study received funding from Lava Therapeutics NV. LK, MJ and MV were funded by LAVA Therapeutics NV., (Copyright © 2024 King, de Jong, Veth, Lutje Hulsik, Yousefi, Iglesias-Guimarais, van Helden, de Gruijl and van der Vliet.)

Background: Despite considerable advancements in cancer immunotherapy, advanced melanoma still presents a substantial clinical challenge. In an effort to explore treatment options, we examined the immunotherapeutic potential of effector Vγ9Vδ2-T cells in vitro in a three-dimensional (3D) human organotypic melanoma-in-skin (Mel-RhS) model., Materials and Methods: Vγ9Vδ2-T cells were introduced into Mel-RhS via intradermal injection and cultured within the tissue microenvironment for up to 3 days., Results: Vγ9Vδ2-T cells remained viable for up to 3 days and were in close proximity to or within tumor nests. Upon Mel-RhS dissociation, a fraction was shown to be decorated by melanoma-associated chondroitin sulfate proteoglycan (MCSP), demonstrating their ability to actively navigate the tumor microenvironment and trogocytose cancer cells. Investigation into the apparent trogocytosis revealed an enhanced activated state of MCSP-decorated Vγ9Vδ2-T cells, evidenced by increased expression levels of 4-1BB, NKp44, programmed cell death protein-1 (PD-1), and programmed death-ligand 1 (PD-L1), compared with their MCSP - counterpart. These findings suggest that Vγ9Vδ2-T cells, upon successfully contacting melanoma cells, actively recognize and acquire MCSP from these malignant cells. Evidence of actual tumor cell elimination, although not significant, was only obtained after preincubation of Mel-RhS with pamidronate, a phosphoantigen-inducing agent, indicating the need for additional T cell receptor-mediated signaling for Vγ9Vδ2-T cells to reach their full oncolytic potential., Conclusions: This study highlights the viability and persistence of Vγ9Vδ2-T cells within the 3D microenvironment, their migratory and antitumor functionality, and the suitability of the model for testing T cell-based therapies, contributing both to the understanding of Vγ9Vδ2-T cell biology and their application in cancer immunotherapy., (© 2024 The Author(s).)

Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is an enveloped DNA virus of the Baculoviridae family. This baculovirus is widely exploited for the biological control of insect pest species and as an expression platform to produce recombinant proteins in insect cells. Extracellular vesicles (EVs) are secreted by all cells and are involved in key roles in many biological processes through their cargo consisting of proteins, RNA or DNA. In viral infections, EVs have been found to transfer both viral and cellular cargo that can elicit either a pro- or antiviral response in recipient cells. Here, small EVs (sEVs) released by Spodoptera frugiperda (Sf) insect cells were characterised for the first time. Using S. frugiperda (SfC1B5) cells stably expressing the baculovirus gp64 , the viral envelope protein GP64 was shown to be incorporated into sEVs. Sf9 cells were also transfected with a bacmid AcMNPV genome lacking p6.9 (AcΔP6.9) to prevent budded virus production. The protein content of sEVs from both mock- and AcΔP6.9-transfected cells were analysed by mass spectrometry. In addition to GP64, viral proteins Ac-F, ME-53 and viral ubiquitin were identified, as well as many host proteins including TSG101-which may be useful as a protein marker for sEVs., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Journal of Extracellular Biology published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

The design and development of supported catalysts for the oxygen evolution reaction (OER) is a promising pathway to reducing iridium loading in proton exchange membrane water electrolysers. However, supported catalysts often suffer from poor activity and durability, particularly when deployed in membrane electrode assemblies. In this work, we deploy iridium coated hollow titanium dioxide particles as OER catalysts to achieve higher Ir mass activities than the leading commercial catalysts. Critically, we demonstrate state-of-the-art durabilities for supported iridium catalysts when compared against the previously reported values for analogous device architectures, operating conditions and accelerated stress test profiles. Through extensive materials characterisations alongside rotating disk electrode measurements, we investigate the role of conductivity, morphology, oxidation state and crystallinity on the OER electrochemical performance. Our work highlights a new supported catalyst design that unlocks high-performance OER activity and durability in commercially relevant testing configurations., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background and Purpose: The Functional Gait Assessment (FGA) and High Level Mobility Assessment Tool (HiMAT) are clinical batteries used to assess people with mild traumatic brain injury (mTBI). However, neither assessment was specifically developed for people with mTBI; the FGA was developed to evaluate vestibular deficits, and the HiMAT was developed for individuals with more severe TBI. To maximize the sensitivity and reduce the time burden of these assessments, the purpose of this study was to determine the combination of FGA and HiMAT items that best discriminates persons with persistent symptoms from mTBI from healthy controls., Methods: Fifty-three symptomatic civilians with persistent symptoms from mTBI (21% male, aged 31 (9.5) years, 328 [267] days since concussion) and 57 healthy adults (28% male, aged 32 (9.6) years) participated across 3 sites. The FGA and HiMAT were evaluated sequentially as part of a larger study. To determine the best combination of items, a lasso-based generalized linear model (glm) was fit to all data., Results: The area under the curve (AUC) for FGA and HiMAT total scores was 0.68 and 0.66, respectively. Lasso regression selected 4 items, including FGA Gait with Horizontal Head Turns and with Pivot Turn, and HiMAT Fast Forward and Backward Walk, and yielded an AUC (95% confidence interval) of 0.71 (0.61-0.79) using standard scoring., Discussion and Conclusions: The results provide initial evidence supporting a reduced, 4-Item Hybrid Assessment of Mobility for mTBI (HAM-4-mTBI) for monitoring individuals with mTBI. Future work should validate the HAM-4-mTBI and investigate its utility for tracking progression throughout rehabilitation.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A409 )., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Academy of Neurologic Physical Therapy, APTA.)

Although supervised and real-time telerehabilitation by videoconferencing is now becoming common for people with Parkinson's disease (PD), its efficacy for balance and gait is still unclear. This paper uses a scoping approach to review the current evidence on the effects of telerehabilitation by videoconferencing on balance and gait for patients with PD. We also explored whether studies have used wearable technology during telerehabilitation to assess and treat balance and gait via videoconferencing. Literature searches were conducted using PubMed, ISI's Web of Knowledge, Cochrane's Library, and Embase. The data were extracted for study design, treatment, and outcomes. Fourteen studies were included in this review. Of these, seven studies investigated the effects of telerehabilitation (e.g., tele-yoga and adapted physiotherapy exercises) on balance and gait measures (e.g., self-reported balance, balance scale, walking speed, mobility, and motor symptoms) using videoconferencing in both assessment and treatment. The telerehabilitation programs by videoconferencing were feasible and safe for people with PD; however, the efficacy still needs to be determined, as only four studies had a parallel group. In addition, no study used wearable technology. Robust evidence of the effects of telerehabilitation by videoconferencing on balance and gait for patients with PD was not found, suggesting that future powered, prospective, and robust clinical trials are needed.

Background: Concussions result in transient symptoms stemming from a cortical metabolic energy crisis. Though this metabolic energy crisis typically resolves in a month, symptoms can persist for years. The symptomatic period is associated with gait dysfunction, the cortical underpinnings of which are poorly understood. Quantifying prefrontal cortex (PFC) activity during gait may provide insight into post-concussion gait dysfunction. The purpose of this study was to explore the effects of persisting concussion symptoms on PFC activity during gait. We hypothesized that adults with persisting concussion symptoms would have greater PFC activity during gait than controls. Within the concussed group, we hypothesized that worse symptoms would relate to increased PFC activity during gait, and that increased PFC activity would relate to worse gait characteristics., Methods: The Neurobehavior Symptom Inventory (NSI) characterized concussion symptoms. Functional near-infrared spectroscopy quantified PFC activity (relative concentration changes of oxygenated hemoglobin [HbO 2 ]) in 14 people with a concussion and 25 controls. Gait was assessed using six inertial sensors in the concussion group., Results: Average NSI total score was 26.4 (13.2). HbO 2 was significantly higher ( P = .007) for the concussed group (0.058 [0.108]) compared to the control group (-0.016 [0.057]). Within the concussion group, HbO 2 correlated with NSI total symptom score (ρ = .62; P = .02), sagittal range of motion ( r = .79; P = .001), and stride time variability ( r = -.54; P = .046)., Conclusion: These data suggest PFC activity relates to symptom severity and some gait characteristics in people with persistent concussion symptoms. Identifying the neurophysiological underpinnings to gait deficits post-concussion expands our knowledge of motor behavior deficits in people with persistent concussion symptoms., 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.

Thematically grouped symptom clusters are present during the acute timeline of post-mild traumatic brain injuries (mTBI), representing clinical profiles called subtypes. Exercise intolerance has not been evaluated within the subtype classifications and, because guidelines support early submaximal aerobic exercise, further knowledge is required in regard to the exercise capabilities among the concussion subtypes. This cross-sectional study ( n  = 78) aimed to characterize the presence of exercise intolerance within the clinical subtypes and to explore performance on the Buffalo Concussion Treadmill Test (BCTT) in the adult subacute (2-12 weeks post-injury) mTBI population. All participants were evaluated using the BCTT to determine exercise tolerance. We first used the Neurobehavioral Symptom Inventory (NSI) questionnaire to assign each participant a primary subtype(s). To further explore all five subtypes (headache, cognitive, vestibular, ocular motor, and mood), participants were assessed using a multitude of thematically grouped assessments including self-reported questionnaires, clinical tests of vestibular and ocular motor function, balance function, and computerized cognitive testing. Thirty-seven (47%) subjects were exercise tolerant and 41 (53%) were exercise intolerant. There was no difference in the distribution of primary subtypes between the exercise tolerant and exercise intolerant groups. In addition, no significant differences were found between the exercise tolerant and exercise intolerant groups on other thematically grouped subtype assessments. The exercise intolerant group had a significantly higher resting heart rate (HR), lower percentage of age-predicted maximum HR achieved, lower Borg Rate of Perceived Exertion (RPE), and could walk on the treadmill for less time (lower duration) compared with the exercise tolerant group. The current findings suggest that exercise intolerance is common and pervasive across all five mTBI subtypes. A comprehensive mTBI assessment should include evaluation for exercise intolerance regardless of the primary clustering of symptoms and across patient populations. Therefore, early referral to physical therapists, athletic trainers, or medical clinics that can perform the BCTT may be helpful to initiate appropriate exercise prescriptions for patients with mTBI.

γδ T cells are important components of the immune system due to their ability to elicit a fast and strong response against infected and transformed cells. Because they can specifically and effectively kill target cells in an MHC independent fashion, there is great interest to utilize these cells in anti-tumor therapies where antigen presentation may be hampered. Since only a small fraction of T cells in the blood or tumor tissue are γδ T cells, they require extensive expansion to allow for fundamental, preclinical and ex vivo research. Although expansion protocols can be successful, most are based on depletion of other cell types rather than γδ T cell specific isolation, resulting in unpredictable purity of the isolated fraction. Moreover, the primary focus only lies with expansion of Vδ2 + T cells, while Vδ1 + T cells likewise have anti-tumor potential. Here, we investigated whether γδ T cells directly isolated from blood could be efficiently expanded while maintaining function. γδ T cell subsets were isolated using MACS separation, followed by FACS sorting, yielding >99% pure γδ T cells. Isolated Vδ1 + and Vδ2 + T cells could effectively expand immediately after isolation or upon freeze/thawing and reached expansion ratios between 200 to 2000-fold starting from varying numbers using cytokine supported feeder stimulations. MACS/FACS isolated and PHA stimulated γδ T cells expanded as good as immobilized antibody mediated stimulated cells in PBMCs, but delivered purer cells. After expansion, potential effector functions of γδ T cells were demonstrated by IFN-γ, TNF-α and granzyme B production upon PMA/ionomycin stimulation and effective killing capacity of multiple tumor cell lines was confirmed in killing assays. In conclusion, pure γδ T cells can productively be expanded while maintaining their anti-tumor effector functions against tumor cells. Moreover, γδ T cells could be expanded from low starting numbers suggesting that this protocol may even allow for expansion of cells extracted from tumor biopsies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Verkerk, Pappot, Jorritsma, King, Duurland, Spaapen and van Ham.)

After a mild traumatic brain injury (mTBI), dizziness and balance problems are frequently reported, affecting individuals' daily lives and functioning. Vestibular rehabilitation is a standard treatment approach for addressing these issues, but its efficacy in this population remains inconclusive. A potential reason for suboptimal outcomes is the lack of objective monitoring of exercise performance, which is crucial for therapeutic success. This study utilized wearable inertial measurement units (IMUs) to quantify exercise performance in individuals with mTBI during home-based vestibular rehabilitation exercises. Seventy-three people with mTBI and fifty healthy controls were enrolled. Vestibular exercises were performed, and IMUs measured forehead and sternum velocities and range of motions. The mTBI group demonstrated a slower forehead peak angular velocity in all exercises, which may be a compensatory strategy to manage balance issues or symptom exacerbation. Additionally, the mTBI group exhibited a larger forehead range of motion during specific exercises, potentially linked to proprioceptive deficits. These findings emphasize the usefulness of utilizing IMUs to monitor the quality of home-based vestibular exercises for individuals with mTBI and the potential for IMUs improving rehabilitation outcomes.

Background: Balance impairments, that lead to falls, are one of the main symptoms of Parkinson's disease (PD). Telerehabilitation is becoming more common for people with PD; however, balance is particularly challenging to assess and treat virtually. The feasibility and efficacy of virtual assessment and virtual treatment of balance in people with PD are unknown. The present study protocol has three aims: I) to determine if a virtual balance and gait assessment (instrumented L-shape mobility test) with wearable sensors can predict a gold-standard, in-person clinical assessment of balance, the Mini Balance Evaluation Systems Test (Mini-BESTest); II) to explore the effects of 12 sessions of balance telerehabilitation and unsupervised home exercises on balance, gait, executive function, and clinical scales; and III) to explore if improvements after balance telerehabilitation transfer to daily-life mobility, as measured by instrumented socks with inertial sensors worn for 7 days., Methods: The TelePD Trial is a prospective, single-center, parallel-group, single-blind, pilot, randomized, controlled trial. This trial will enroll 80 eligible people with PD. Participants will be randomized at a 1:1 ratio into receiving home-based balance exercises in either: 1) balance telerehabilitation (experimental group, n = 40) or 2) unsupervised exercises (control group, n = 40). Both groups will perform 12 sessions of exercise at home that are 60 min long. The primary outcome will be Mini-BESTest. The secondary outcomes will be upper and lower body gait metrics from a prescribed task (instrumented L-shape mobility test); daily-life mobility measures over 7 days with wearable sensors in socks, instrumented executive function tests, and clinical scales. Baseline testing and 7 days of daily-life mobility measurement will occur before and after the intervention period., Conclusion: The TelePD Trial will be the first to explore the usefulness of using wearable sensor-based measures of balance and gait remotely to assess balance, the feasibility and efficacy of balance telerehabilitation in people with PD, and the translation of balance improvements after telerehabilitation to daily-life mobility. These results will help to develop a more effective home-based balance telerehabilitation and virtual assessment that can be used remotely in people with balance impairments., Trial Registration: This trial was prospectively registered on ClinicalTrials.gov (NCT05680597)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Imbalance is common following mild Traumatic Brain Injury (mTBI) and can persist months after the initial injury. To determine if mTBI subjects with chronic imbalance differed from healthy age- and sex-matched controls (HCs) we used both the Central SensoriMotor Integration (CSMI) test, which evaluates sensory integration, time delay, and motor activation properties and the standard Sensory Organization Test (SOT). Four CSMI conditions evoked center-of-mass sway in response to: surface tilts with eyes closed (SS/EC), surface tilts with eyes open viewing a fixed visual surround (SS/EO), visual surround tilts with eyes open standing on a fixed surface (VS/EO), and combined surface and visual tilts with eyes open (SS+VS/EO). The mTBI participants relied significantly more on visual cues during the VS/EO condition compared to HCs but had similar reliance on combinations of vestibular, visual, and proprioceptive cues for balance during SS/EC, SS/EO, and SS+VS/EO conditions. The mTBI participants had significantly longer time delays across all conditions and significantly decreased motor activation relative to HCs across conditions that included surface-tilt stimuli with a sizeable subgroup having a prominent increase in time delay coupled with reduced motor activation while demonstrating no vestibular sensory weighting deficits. Decreased motor activation compensates for increased time delay to maintain stability of the balance system but has the adverse consequence that sensitivity to both internal (e.g., sensory noise) and external disturbances is increased. Consistent with this increased sensitivity, SOT results for mTBI subjects showed increased sway across all SOT conditions relative to HCs with about 45% of mTBI subjects classified as having an "Aphysiologic" pattern based on published criteria. Thus, CSMI results provided a plausible physiological explanation for the aphysiologic SOT pattern. Overall results suggest that rehabilitation that focuses solely on sensory systems may be incomplete and may benefit from therapy aimed at enhancing rapid and vigorous responses to balance perturbations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Campbell, King, Parrington, Fino, Antonellis and Peterka.)

Complaints of non-resolving imbalance are common in individuals with chronic mild traumatic brain injury (mTBI). Vestibular rehabilitation therapy may be beneficial for this population. Additionally, wearable sensors can enable biofeedback, specifically audio biofeedback (ABF), and aid in retraining balance control mechanisms in people with balance impairments. In this study, we described the effectiveness of vestibular rehabilitation therapy with and without ABF to improve balance in people with chronic mTBI. Participants ( n = 31; females = 22; mean age = 40.9 ± 11 y) with chronic (>3 months) mTBI symptoms of self-reported imbalance were randomized into vestibular rehabilitation with ABF ( n = 16) or without ABF ( n = 15). The intervention was a standard vestibular rehabilitation, with or without ABF, for 45 min biweekly for 6 weeks. The ABF intervention involved a smartphone that provided auditory feedback when postural sway was outside of predetermined equilibrium parameters. Participant's completed the Post-Concussion Symptom Scale (PCSS). Balance was assessed with the sensory organization test (SOT) and the Central Sensorimotor Integration test which measured sensory weighting, motor activation, and time delay with sway evoked by surface and/or visual surround tilts. Effect sizes (Hedge's G) were calculated on the change between pre-and post-rehabilitation scores. Both groups demonstrated similar medium effect-sized decreases in PCSS and large increases in SOT composite scores after rehabilitation. Effect sizes were minimal for increasing sensory weighting for both groups. The with ABF group showed a trend of larger effect sizes in increasing motor activation (with ABF = 0.75, without ABF = 0.22) and in decreasing time delay (with ABF = -0.77, without ABF = -0.52) relative to the without ABF group. Current clinical practice focuses primarily on sensory weighting. However, the evaluation and utilization of motor activation factors in vestibular rehabilitation, potentially with ABF, may provide a more complete assessment of recovery and improve outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Campbell, Peterka, Fino, Parrington, Wilhelm, Pettigrew and King.)

Background and Purpose: Multimodal physical therapy for mild traumatic brain injury (mTBI) has been shown to improve recovery. Due to the coronavirus disease-2019 (COVID-19) pandemic, a clinical trial assessing the timing of multimodal intervention was adapted for telerehabilitation. This pilot study explored feasibility and adoption of an in-person rehabilitation program for subacute mTBI delivered through telerehabilitation., Methods: Fifty-six in-person participants-9 males; mean (SD) age 34.3 (12.2); 67 (31) days post-injury-and 17 telerehabilitation participants-8 males; age 38.3 (12.7); 61 (37) days post-injury-with subacute mTBI (between 2 and 12 weeks from injury) were enrolled. Intervention included 8, 60-minute visits over 6 weeks and included subcategories that targeted cervical spine, cardiovascular, static balance, and dynamic balance impairments. Telerehabilitation was modified to be safely performed at home with minimal equipment. Outcome measures included feasibility (the number that withdrew from the study, session attendance, home exercise program adherence, adverse events, telerehabilitation satisfaction, and progression of exercises performed), and changes in mTBI symptoms pre- and post-rehabilitation were estimated with Hedges' g effect sizes., Results: In-person and telerehabilitation had a similar study withdrawal rate (13% vs 12%), high session attendance (92% vs 97%), and no adverse events. The telerehabilitation group found the program easy to use (4.2/5), were satisfied with care (4.7/5), and thought it helped recovery (4.7/5). The telerehabilitation intervention was adapted by removing manual therapy and cardiovascular portions and decreasing dynamic balance exercises compared with the in-person group. The in-person group had a large effect size (-0.94) in decreases in symptoms following rehabilitation, while the telerehabilitation group had a moderate effect size (-0.73)., Discussion and Conclusions: Telerehabilitation may be feasible for subacute mTBI. Limited ability to address cervical spine, cardiovascular, and dynamic balance domains along with underdosage of exercise progression may explain group differences in symptom resolution.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A392 )., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Academy of Neurologic Physical Therapy, APTA.)

Background and Aim: Individuals with Parkinson's disease (PD) with and without freezing of Gait (FoG) may respond differently to exercise interventions for several reasons, including disease duration. This study aimed to determine whether both people with and without FoG benefit from the Agility Boot Camp with Cognitive Challenges (ABC-C) program., Methods: This secondary analysis of our ABC-C trial included 86 PD subjects: 44 without FoG (PD-FoG) and 42 with FoG (PD + FoG). We collected measures of standing sway balance, anticipatory postural adjustments, postural responses, and a 2-minute walk with and without a cognitive task. Two-way repeated analysis of variance, with disease duration as covariate, was used to investigate the effects of ABC-C program. Effect sizes were calculated using standardized response mean (SRM) for PD-FoG and PD + FoG, separately., Results: The ABC-C program was effective in improving gait performance in both PD-FoG and PD + FoG, even after controlling for disease duration. Specifically, dual-task gait speed ( P  < .0001), dual-cost stride length ( P  = .012), and these single-task measures: arm range of motion ( P  < .0001), toe-off angle ( P  = .005), gait cycle duration variability ( P  = .019), trunk coronal range of motion ( P  = .042), and stance time ( P  = .046) improved in both PD-FoG and PD + FoG. There was no interaction effect between time (before and after exercise) and group (PD-FoG/PD + FoG) in all 24 objective measures of balance and gait. Dual-task gait speed improved the most in PD + FoG (SRM = 1.01), whereas single-task arm range of motion improved the most in PD-FoG (SRM = 1.01)., Conclusion: The ABC-C program was similarly effective in improving gait (and not balance) performance in both PD-FoG and PD + FoG.

γδ T-cells directly recognize and kill transformed cells independently of HLA-antigen presentation, which makes them a highly promising effector cell compartment for cancer immunotherapy. Novel γδ T-cell-based immunotherapies, primarily focusing on the two major γδ T-cell subtypes that infiltrate tumors ( i.e. Vδ1 and Vδ2), are being developed. The Vδ1 T-cell subset is enriched in tissues and contains both effector T-cells as well as regulatory T-cells with tumor-promoting potential. Vδ2 T-cells, in contrast, are enriched in circulation and consist of a large, relatively homogeneous, pro-inflammatory effector T-cell subset. Healthy individuals typically harbor in the order of 50-500 million Vγ9Vδ2 T-cells in the peripheral blood alone (1-10% of the total CD3 + T-cell population), which can rapidly expand upon stimulation. The Vγ9Vδ2 T-cell receptor senses intracellular phosphorylated metabolites, which accumulate in cancer cells as a result of mevalonate pathway dysregulation or upon pharmaceutical intervention. Early clinical studies investigating the therapeutic potential of Vγ9Vδ2 T-cells were based on either ex vivo expansion and adoptive transfer or their systemic activation with aminobisphosphonates or synthetic phosphoantigens, either alone or combined with low dose IL-2. Immune-related adverse events (irAE) were generally \mild, but the clinical efficacy of these approaches provided overall limited benefit. In recent years, critical advances have renewed the excitement for the potential of Vγ9Vδ2 T-cells in cancer immunotherapy. Here, we review γδ T-cell-based therapeutic strategies and discuss the prospects of those currently evaluated in clinical studies in cancer patients as well as future therapies that might arise from current promising pre-clinical results., Competing Interests: JS-E, MJ and LK are funded by Lava therapeutics. HV, PP, EE, BW are employed by and hold stock of LAVA Therapeutics. TG holds stock of LAVA Therapeutics., (Copyright © 2022 Saura-Esteller, de Jong, King, Ensing, Winograd, de Gruijl, Parren and van der Vliet.)

Background: Physical function remains a crucial component of mild traumatic brain injury (mTBI) assessment and recovery. Traditional approaches to assess mTBI lack sensitivity to detect subtle deficits post-injury, which can impact a patient's quality of life, daily function and can lead to chronic issues. Inertial measurement units (IMU) provide an opportunity for objective assessment of physical function and can be used in any environment. A single waist worn IMU has the potential to provide broad/macro quantity characteristics to estimate gait mobility, as well as more high-resolution micro spatial or temporal gait characteristics (herein, we refer to these as measures of quality). Our recent work showed that quantity measures of mobility were less sensitive than measures of turning quality when comparing the free-living physical function of chronic mTBI patients and healthy controls. However, no studies have examined whether measures of gait quality in free-living conditions can differentiate chronic mTBI patients and healthy controls. This study aimed to determine whether measures of free-living gait quality can differentiate chronic mTBI patients from controls., Methods: Thirty-two patients with chronic self-reported balance symptoms after mTBI (age: 40.88 ± 11.78 years, median days post-injury: 440.68 days) and 23 healthy controls (age: 48.56 ± 22.56 years) were assessed for ~ 7 days using a single IMU at the waist on a belt. Free-living gait quality metrics were evaluated for chronic mTBI patients and controls using multi-variate analysis. Receiver operating characteristics (ROC) and Area Under the Curve (AUC) analysis were used to determine outcome sensitivity to chronic mTBI., Results: Free-living gait quality metrics were not different between chronic mTBI patients and controls (all p > 0.05) whilst controlling for age and sex. ROC and AUC analysis showed stride length (0.63) was the most sensitive measure for differentiating chronic mTBI patients from controls., Conclusions: Our results show that gait quality metrics determined through a free-living assessment were not significantly different between chronic mTBI patients and controls. These results suggest that measures of free-living gait quality were not impaired in our chronic mTBI patients, and/or, that the metrics chosen were not sensitive enough to detect subtle impairments in our sample., (© 2022. The Author(s).)

Objective: To explore patterns of postconcussion care at a level 1 trauma center., Design: Retrospective cohort study., Setting: U.S. level 1 trauma center and local satellite units., Participants: Patients of any age with a concussion diagnosis that reported to level 1 trauma center and local satellite units between 2016 and 2018 (N=2417)., Intervention: Not applicable., Main Outcome Measures: Age, sex, point of entry, rehabilitation referrals, and pre-existing comorbidity diagnosis., Results: Patient age (mean [SD]) significantly differed among points of entry, from youngest to oldest: 26.0 (14.0) years in sports medicine, 29.3 (23.0) years in the emergency department, 34.6 (23.6) years at primary care providers, and 46.0 (19.7) years at specialty care departments. Sex also significantly differed among points of entry; emergency departments reported more men (55.6%), whereas the other points of entry reported more women (59.3%-65.6%). Patients were more likely to receive a referral from sports medicine (odds ratio [OR] unadjusted =75.05, P <.001), primary care providers (OR unadjusted =7.98, P <.001), and specialty care departments (OR unadjusted =7.62, P <.001) than from the emergency department. Women were more likely to receive a referral (OR unadjusted =1.92, P <.0001), regardless of point of entry. Lastly, patients with a preexisting comorbidity were more likely (OR adjusted =2.12, P <.001) to get a rehabilitation referral than patients without a comorbidity., Conclusions: Point of entry, age, sex, and preexisting comorbidities are associated with postconcussion care rehabilitation referral patterns. Improving concussion education dissemination across all entry points of a level 1 trauma center may standardize the postconcussion rehabilitation referral patterns, potentially improving the time to recovery from a concussion., (© 2022 The Authors.)

The ability to kill tumor cells while maintaining an acceptable safety profile makes Natural Killer (NK) cells promising assets for cancer therapy. Strategies to enhance the preferential accumulation and activation of NK cells in the tumor microenvironment can be expected to increase the efficacy of NK cell-based therapies. In this study, we show binding of a novel bispecific single domain antibody (VHH) to both CD16 (FcRγIII) on NK cells and the epidermal growth factor receptor (EGFR) on tumor cells of epithelial origin. The bispecific VHH triggered CD16- and EGFR-dependent activation of NK cells and subsequent lysis of tumor cells, regardless of the KRAS mutational status of the tumor. Enhancement of NK cell activation by the bispecific VHH was also observed when NK cells of colorectal cancer (CRC) patients were co-cultured with EGFR expressing tumor cells. Finally, higher levels of cytotoxicity were found against patient-derived metastatic CRC cells in the presence of the bispecific VHH and autologous peripheral blood mononuclear cells or allogeneic CD16 expressing NK cells. The anticancer activity of CD16-EGFR bispecific VHHs reported here merits further exploration to assess its potential therapeutic activity either alone or in combination with adoptive NK cell-based therapeutic approaches.

Five studies tested the effect of exposure to authoritarian values on positive affect (PA), negative affect (NA), and meaning in life (MIL). Study 1 (N = 1,053) showed that simply completing a measure of right-wing authoritarianism (vs. not) prior to rating MIL led to higher MIL. Preregistered Study 2 (N = 1,904) showed that reading speeches by real-world authoritarians (e.g., Adolf Hitler) led to lower PA, higher NA, and higher MIL than a control passage. In preregistered Studies 3 (N = 1,573) and 4 (N = 1,512), Americans read authoritarian, egalitarian, or control messages and rated mood, MIL, and evaluated the passages. Both studies showed that egalitarian messages led to better mood and authoritarian messages led to higher MIL. Study 5 (N = 148) directly replicated these results with Canadians. Aggregating across studies (N = 3,401), moderational analyses showed that meaning in life, post manipulation, was associated with more favorable evaluations of the authoritarian passage. In addition, PA was a stronger predictor of MIL in the egalitarian and control conditions than in the authoritarian condition. Further results showed no evidence that negative mood (or disagreement) spurred the boost in MIL. Implications and future directions are discussed., Competing Interests: The authors have declared that no competing interests exist.