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Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoproliferative disorders arising from mature T cells, accounting for about 10% of non-Hodgkin lymphomas. PTCL-not otherwise specified is the most common subtype, followed by angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, anaplastic lymphoma kinase–positive, anaplastic large cell lymphoma, anaplastic lymphoma kinase–negative, and enteropathy-associated T-cell lymphoma. This discussion section focuses on the diagnosis and treatment of PTCLs as outlined in the NCCN Guidelines for T-Cell Lymphomas.

Background: HER2 is overexpressed in different solid tumors, including 10-20% breast and gastric cancers. Many HER2-targeted drugs, including trastuzumab, pertuzumab, lapatinib, trastuzumab emtansine (T-DM1), and trastuzumab deruxtecan (T-DXd), have been approved for treatment of HER2-positive early and metastatic breast cancer (BC). However, trials involving pertuzumab, lapatinib and T-DM1 have failed to provide significant clinical improvements in patients with HER2-positive gastric cancer (GC), suggesting differences in HER2 mediated disease biology between HER2-positive BC and GC. Recent studies have suggested efficacy of HER2 antibodies could be further enhanced by antibody-dependent cellular phagocytosis (ADCP) principally regulated by “don’t-eat-me” CD47 signals, which is overexpressed in many HER2-positive cancers and suppresses phagocytosis through binding to SIRPα. Methods: BC and GC cell lines were used. Monocytes were isolated from human PBMC and differentiated into macrophages, which were used for in vitro ADCP assays. In in vivo animal experiments, D3L-001 and comparator antibodies were examined for efficacy in solid tumor xenograft models. Results: D3L-001 was designed to have higher HER2 affinity (KD < 1 nM) than that of CD47 (KD >10 nM). With this unique design, D3L-001 showed preferential binding to HER2/CD47 double positive tumor cells as compared to CD47 single positive cells. D3L-001 showed better anti-tumor effect than trastuzumab in a panel of solid tumor models, including but not limited to BC and GC cell lines or patient derived xenografts. Immunohistochemistry (IHC) analysis was performed in tumor FFPE slides to evaluate expression of HER2 and CD47 in the efficacy tested models, and we observed that D3L-001 showed broad tumor growth inhibition in HER2 or CD47 high/low expression models. In both in vitro and in vivo studies using breast cancer HCC1954, JIMT-1 and gastric cancer N87 models, we observed a synergistic effect in the combination of Trastuzumab with Magrolimab. Moreover, D3L-001 showed a trend of better efficacy than the combination of Trastuzumab and Magrolimab. These results confirm the synergistic effect of dual-targeting HER2 and CD47 simultaneously and suggest advantage of using bispecific antibodies to confer such effect. D3L-001 also displayed potent and comparable in vivo efficacy as Enhertu in gastric N87 model, and it showed synergistic in vivo efficacy, when combining with Pertuzumab or Paclitaxel, in breast HCC1954, JIMT-1 and gastric cancer N87 models. Conclusion: D3L-001, a novel HER2×CD47 bsAb, demonstrated potent anti-tumor effect in a variety of solid tumor models via HER2 guided CD47 co-blocking. It also showed synergistic efficacy when combining with other anti-tumor agents. D3L-001 will be further evaluated in clinic for its potential as a novel treatment option in HER2-positive BC, GC and other solid tumors. Citation Format: Haopeng Rui, Xiaofeng Yang, Jiahao Chen, Jia Wang, Zhiqiang Zheng, Zhiqiang Chen, Jingtao Lu, Peggy Wu, Janet Chen, Allison Wang, George Chen. D3L-001, a novel bispecific antibody targeting HER2 and CD47, demonstrates potent preclinical efficacy in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1873.

Computer-mediated communications (CMC) can be used as a substitute for face-to-face (FtF) meetings but their effectiveness is highly context dependent. This paper describes a theoretical framework and initial experimental design for characterizing a travel replacement threshold. This effort begins with a use case of remote engineering maintenance training, conducted in three conditions: side-by-side (physically proximate), teleconference (using off-the-shelf software), and a custom VR/AR system designed to provide the apprentice with a virtual view of both the instructor’s larger scale lab and smaller scale workbench. The research hypotheses, experimental protocol, and dependent measures are described. The task involves an instructor demonstrating a circuit board troubleshooting task to a remote apprentice. The apprentice then completes the trained task independently, and performance and subject preferences are compared across conditions. The details of this paper, the result of extensive literature review and winnowing of variables, may assist researchers exploring CMC, training, or social communication.

Objectives Vitamin D (25(OH)D) deficiency and metabolic syndrome (MetS) may both contribute to increased cardiovascular risk in SLE. We aimed to examine the association of demographic factors, SLE phenotype, therapy and vitamin D levels with MetS and insulin resistance. Methods The Systemic Lupus International Collaborating Clinics (SLICC) enrolled patients recently diagnosed with SLE ( Results Of the 1847 patients, 1163 (63%) had vitamin D measured and 398 (34.2%) subjects were in the lowest 25(OH)D tertile. MetS was present in 286 of 860 (33%) patients whose status could be determined. Patients with lower 25(OH)D were more likely to have MetS and higher HOMA-IR. The MetS components, hypertension, hypertriglyceridemia and decreased high-density lipoprotein (HDL) were all significantly associated with lower 25(OH)D. Increased average glucocorticoid exposure was associated with higher insulin resistance. Conclusions MetS and insulin resistance are associated with lower vitamin D in patients with SLE. Further studies could determine whether vitamin D repletion confers better control of these cardiovascular risk factors and improve long-term outcomes in SLE.

Purpose This open-label, single-dose study evaluated the pharmacokinetic profiles of enzalutamide and its major metabolites and the safety of enzalutamide in healthy, Chinese male volunteers. Methods Fourteen volunteers (median age, 28.5 years) received a single oral dose of enzalutamide (160 mg) under fasting conditions on day 1 and were followed for 50 days. Pharmacokinetic profiles were obtained for enzalutamide and its major metabolites, carboxylic acid metabolite (M1; inactive metabolite) and N-desmethyl enzalutamide (M2; active metabolite), on day 1 up to 1176 hours (49 days). Safety data were also collected. Findings Enzalutamide plasma concentration rapidly increased (median Tmax, 1.5 hours) followed by a slow decrease (mean t½, 90.7 hours). M1 and M2 plasma concentrations increased gradually with a median Tmax of 72.0 and 121 hours, respectively. M1 and M2 mean metabolite-to-parent ratios were 0.2 and 1.3, respectively. Mean AUC0–∞ of enzalutamide plus M2 was 828 μg h/mL versus 368 μg h/mL for enzalutamide alone. Mean t½, maximum concentration, and Tmax of enzalutamide plus M2 were comparable with those of enzalutamide. Drug-related treatment-emergent adverse events were reported in 4 men (28.6%): 1 each of upper respiratory tract infection, chest discomfort, increased blood bilirubin, and decreased white blood cell count. No deaths or serious treatment-emergent adverse events were observed. Implications The pharmacokinetic profiles of enzalutamide, M1, M2, and enzalutamide plus M2 in healthy Chinese men were generally consistent with those in white men. No new safety concerns were found. Chinese Clinical Trial Registration identifier: CTR20150635.

Business travel leads to the consumption of large amounts of energy. Circuit World (CW), a Unity virtual environment, uses avatars and realistic simulations of electrical circuits to test the effectiveness of teaching complex engineering tasks without travel. To evaluate CW, a study compares how well participants learn to repair a circuit when trained face-to-face, via Zoom, and within CW wearing an HMD. After training and completion of a knowledge quiz, learners are given a circuit to repair by themselves using a non-immersive desktop version of CW. Participants repair it again two weeks later to test retention. Each study session involves three people: learner, trainer, and researcher. The learner and trainer control avatars and the researcher, invisible, observes over the learner’s shoulder. Collected data includes task performance logs from CW, knowledge quiz scores, and, based on video recordings, eye gaze tracking, behavioral coding, and measures of facial synchrony between trainer and learner.

Long duration exploration missions present unique challenges to the behavioral health of astronauts. Factors like isolation, social monotony, extreme living conditions, chronic stress, and interpersonal differences within the team can affect both crew wellbeing and performance. Therefore, we have developed a VR environments and VR games to study team dynamics, cooperation and cohesion among crew members. We have tested this game during 12- and 8-month long space flight simulation studies at the Hawaii Space Exploration Analog and Simulation (HI-SEAS) facilities in Waimea, HI, where subjects underwent adjustments in physiology and lifestyle that are analogous to some of the challenges in a confined environment (HI-SEAS.org). The goal of this work supports NASA's goals to “identify and validate measures to monitor behavioral health and performance during autonomous, long duration and/or long distance exploration missions”. Our results indicate that virtual reality can be used as an effective platform and sensor to test the effects of social isolation and monotony on team dynamics during long-duration missions. VR could also be effective for delivering other types of assessments and therapies.

Santiago J Saldana,1 Anthony P Marsh,2 W Jack Rejeski,2 Jack K Haberl,2 Peggy Wu,3 Scott Rosenthal,4 Edward H Ip1 1Department of Biostatistical Sciences, Wake Forest School of Medicine, 2Department of Health and Exercise Science, Wake Forest University, Winston-Salem, NC, 3Research and Development, Smart Information Flow Technologies, Minneapolis, MN, 4Wake Forest School of Medicine, Winston-Salem, NC, USA Introduction: As the population ages, the prevention of falls is an increasingly important public health problem. Balance assessment forms an important component of fall-prevention programs for older adults. The recent development of cost-effective and highly responsive virtual reality (VR) systems means new methods of balance assessment are feasible in a clinical setting. This proof-of-concept study made use of the submillimeter tracking built into modern VR head-mounted displays (VRHMDs) to assess balance through the use of visual–vestibular conflict. The objective of this study was to evaluate the validity, acceptability, and reliability of using a VRHMD to assess balance in older adults.Materials and methods: Validity was assessed by comparing measurements from the VRHMD to measurements of postural sway from a force plate. Acceptability was assessed through the use of the Simulator Sickness Questionnaire pre- and postexposure to assess possible side effects of the visual–vestibular conflict. Reliability was assessed by measuring correlations between repeated measurements 1 week apart. Variables of possible importance that were found to be reliable (r≥0.9) between tests separated by a week were then tested for differences compared to a control group. Assessment was performed as a cross-sectional single-site community center-based study in 13 older adults (≥65 years old, 80.2±7.3 years old, 77% female, five at risk of falls, eight controls). The VR balance assessment consisted of four modules: a baseline module, a reaction module, a balance module, and a seated assessment.Results: There was a significant difference in the rate at which participants with a risk of falls changed their tilt in the anteroposterior direction compared to the control group. Participants with a risk of falls changed their tilt in the anteroposterior direction at 0.7°/second vs 0.4°/second for those without a history of falls. No significant differences were found between pre/postassessment for oculomotor score or total Simulator Sickness Questionnaire score. Both the force plate and the head-mounted display balance-assessment system were able to detect differences between conditions meant to mask visual and proprioceptive information.Conclusion: This VRHMD is both affordable and portable, causes minimal simulator sickness, and produces repeatable results that can be used to assess balance in older adults. Keywords: virtual reality, balance, falls, elderly&nbsp

Background The Organ Procurement Transplant Network (OPTN) registry collects data on posttransplant malignancies in solid organ transplant recipients. Complete and accurate registry data on skin cancer is critical for research on epidemiology and interventions. Objective The study goal was to determine the validity of Organ Procurement Transplant Network skin cancer data. Methods This cohort study compared reporting of posttransplant squamous cell carcinoma (SCC) and malignant melanoma (MM) in OPTN to medical-record review-derived data from the Transplant Skin Cancer Network (TSCN) database. In total, 4934 organ transplant recipients from the TSCN database were linked to patient-level OPTN malignancy data. We calculated sensitivity, specificity, correct classification (CC), positive predictive value (PPV), and negative predictive value (NPV) for SCC and MM reporting in the OPTN database. Results OPTN reporting for SCC (population prevalence 11%) had sensitivity 41%, specificity 99%, PPV 88%, NPV 93%, and CC 93%. OPTN reporting for MM (population prevalence 1%) had sensitivity 22%, specificity 100%, PPV 73%, NPV 99%, and CC 99%. Limitations Only a subset of patients in the TSCN cohort had matched United Network for Organ Sharing cancer registry data for comparison. Conclusion OPTN reporting had poor sensitivity but excellent specificity for SCC and MM. Dermatologists and transplant physicians are encouraged to improve the validity of OPTN skin cancer data through improved communication and reporting.

Team interactions, performance, and cohesion, as well as individual psychosocial states, are increasingly recognized and studied contributions to overall system performance, but few teams will ever live and work together as closely for as long as those supporting proposed deep space missions like those to Mars or the asteroids. Yet studying team dynamics and the factors which affect them during space exploration is extraordinarily challenging since no such team performance data yet exists. The members of this panel are participating in various NASA-sponsored research efforts to explore long duration team interactions in space exploration contexts. The lessons they are learning, as well as the techniques they are developing to study this challenging problem, will serve to inform not only human space exploration over the next few decades, but also team performance and relationships in a wide variety of earth-based domains in which humans must work with each other to accomplish demanding tasks over the long term and/or in Isolated, Confined, and Extreme (ICE) environments.

Patients with SLE have an increased risk of cardiovascular disease at a much earlier age than the general population1. SLE itself has been shown to be an independent risk factor in the progression of atherosclerosis2. The associated morbidity and mortality of cardiovascular disease has prompted the study of subclinical atherosclerosis in the SLE population, as measured with imaging studies such as carotid ultrasound and electron beam computed tomography (CT) scans3. Higher aorta calcium scores (AC) and coronary artery calcification (CAC) have been shown to be more prevalent in SLE patients when compared with age- and sex-matched controls4. CAC has also been shown to occur at a younger age in the SLE population4,5 when compared with controls. Similarly, SLE patients appear to have an accelerated rate of atherosclerosis progression when compared with the general population, however the mechanisms or manner underlying this is not clear. Older age and longer disease duration were associated with carotid plaque progression in an early study6, and in another, after controlling for age, traditional factors including higher LDL levels and current smoking status, as well as SLE-related factors, including higher serum C3 level and higher Systemic Lupus Activity Measure (SLAM) score, were associated with carotid plaque progression7. Carotid intima media thickness (IMT) progression has been associated also with higher serum creatinine, homocysteine level, and C3 level7,8. Kiani et al further investigated cumulative exposure to risk factors in progression of IMT, carotid plaque, and CAC9. In their multivariate analyses, progression in CAC was associated with age, current smoking, and lower high-sensitivity C-reactive protein (hsCRP), but not with SLE disease activity measures. There are very few studies that have investigated risk factors in the progression of CAC and none that have explored risk factors for AC progression in those with SLE. We investigated baseline traditional and SLE-related risk factors in the progression of CAC and AC in women with SLE and in comparison with a control population. We hypothesized that not only would the rate of progression in CAC and AC be greater in those with SLE when compared with controls, but also that the risk factors for progression would differ between the groups. This is the first study to explore progression in AC in women with SLE.

Objective. An association between 25-hydroxyvitamin D (25[ OH] D; vitamin D) deficiency and increased cardiovascular (CV) risk factors and CV disease (CVD) has been shown in general population studies. Vitamin D deficiency has been noted in systemic lupus erythematosus (SLE), and CVD is a major cause of morbidity and mortality in SLE. The objectives of this study were to estimate the associations of 25(OH) D levels with CV risk factors and to determine whether low baseline 25(OH) D levels predict future CV events in patients participating in an international inception cohort. Methods. Data were collected on 890 participants, including demographics, SLE activity and damage assessments, CV risk factors and events, medications, laboratory assessments of 25(OH) D levels, and inflammatory markers. Multiple logistic and Cox regressions were used to estimate the associations of baseline 25(OH) D levels with baseline CV risk factors and CVD events. The models were adjusted for age, sex, race, season, and country, with and without body mass index. Results. Patients in the higher quartiles of 25(OH) D were less likely to have hypertension and hyperlipidemia and were more likely to have lower C-reactive protein levels and lower Systemic Lupus Erythematosus Disease Activity Index 2000 scores at baseline when compared with the first quartile. Vitamin D levels were not independently associated with CVD event incidence; however, hazard ratios for CVD event incidence decreased with successively higher quartiles. Conclusion. Lower baseline 25(OH) D levels are associated with higher risk for CV risk factors and more active SLE at baseline. There may be a trend toward a lower likelihood of CVD events in those with higher baseline 25(OH) D levels. (Less)

Long duration Mars exploration missions will face unprecedented sensory and social monotony that will impact various aspects of space crew performance as well as behavioral health. We describe ANSIBLE --- A Network of Social Interactions for Bilateral Life Enhancement. ANSIBLE is a virtual world ecosystem that implements evidence based strategies to promote social connectedness and psychological well-being, while being extendable and able to accommodate technical and environmental limitations of long duration flight. ANSIBLE was deployed in a twelve month isolation study to evaluate its capacity to maintain the social connection between participants in an isolated Mars simulation analog environment and their friends and family (FF) living outside the habitat. The Mars simulation exercise takes place at the Hawaii Space Exploration Analog and Simulation (HI-SEAS) facilities in Waimea, HI, where subjects undergo adjustments in physiology and lifestyle that are analogous to some of the challenges in a confined environment, with Mars exploration conditions (e.g. with communication latencies and blackouts, in close quarters, under restricted water and energy use). We present preliminary results suggesting that ANSIBLE can increase feelings of closeness as well as satisfaction with FF relationships over traditional methods, as well as promoting continued interactions of FF with crew members, closeness to humanity, decreased stress, and the perception that time is moving fast.

We describe preliminary results of ANSIBLE – A Network of Social Interactions for Bilateral Life Enhancement. ANSIBLE leverages virtual worlds to deliver evidence based wellness promoting strategies and virtual agents as tools to facilitate asynchronous human-human communication in order to counteract behavioral health challenges associated with prolonged isolation and deep space exploration. ANSIBLE was deployed in August 2015 in a 12 month study with six crew members in an isolation simulated Mars habitat facility. In this paper, we compare the data for the first five months of this mission to a previous control mission for which ANSIBLE was not used. We found initial support for ANSIBLE to increase perceptions of closeness and satisfaction with friend and family relationships (but not other crew members) during prolonged isolation as well as a trend in stress reduction and increased feelings of ANSIBLE usability over time.