Polaris Research Articles

Human-centered NLP Fact-checking: Co-Designing with Fact-checkers using Matchmaking for AI

While many Natural Language Processing (NLP) techniques have been proposed for fact-checking, both academic research and fact-checking organizations report limited adoption of such NLP work due to poor alignment with fact-checker practices, values, and needs. To address this, we investigate a co-design method, Matchmaking for AI, to enable fact-checkers, designers, and NLP researchers to collaboratively identify what fact-checker needs should be addressed by technology, and to brainstorm ideas for potential solutions. Co-design sessions we conducted with 22 professional fact-checkers yielded a set of 11 design ideas that offer a "north star'', integrating fact-checker criteria into novel NLP design concepts. These concepts range from pre-bunking misinformation, efficient and personalized monitoring misinformation, proactively reducing fact-checker potential biases, and collaborative writing fact-check reports. Our work provides new insights into both human-centered fact-checking research and practice and AI co-design research.

A Unified Set of Patient-Inspired Health Concepts for COPD: A North Star for Understanding Treatment Benefit.

A Unified Set of Patient-Inspired Health Concepts for COPD: A North Star for Understanding Treatment Benefit.

Rethinking Success: A Stakeholder Approach to Maximize Long-Term Impact and Performance

In an era of heightened global competition, organizational success can no longer rely solely on efficiency, quality, and customer retention. This article makes the case for prioritizing value creation as the new guiding principle, emphasizing the need to generate value not only for shareholders but across all stakeholders—including employees, customers, communities, and the environment. We explore the shift from shareholder-centric models to stakeholder value frameworks, backed by research and practical examples. Key strategies for operationalizing this agenda include aligning business goals with social impact, fostering inclusive cultures, and implementing holistic performance metrics. Case studies of companies like Danone, 3M, and Adobe illustrate how stakeholder-driven approaches unlock sustainable growth, innovation, and social good. Ultimately, organizations that adopt value creation as their north star will be best positioned to achieve both long-term profitability and meaningful impact.

Characterization of patients with Duchenne muscular dystrophy across previously developed health states.

Project HERCULES has developed a natural history model (NHM) of disease progression in Duchenne muscular dystrophy (DMD) that comprises eight ordered health states (two ambulatory states, one transfer state indicating increased caregiver burden in which patients cannot walk/run 10m or rise from floor but can still support their own weight, and five non-ambulatory states). The current study used data from nine sources (clinical trial placebo arms, one real-world dataset, and three natural history datasets) to further characterize patients with DMD according to these health states. The study included 1,173 patients across 5,306‬ visits. Patients were on average older and exhibited worse ambulatory, pulmonary, upper limb, and cardiac functions with each successive health state. Mean±SE ages increased monotonically across health states, starting with 8.47±0.07 for early ambulatory, 10.86±0.13 for late ambulatory, 11.65±0.35 for transfer state, and ranging from 13.17±0.32 to 16.84±0.37 for the non-ambulatory states. North Star Ambulatory Assessment (NSAA) total score, which measures motor function and ranges from 34 (best) to 0 (worst), was 23.7 (interquartile range [IQR]: 20-30) for early ambulatory patients, 12.7 (IQR: 9-16) for late ambulatory patients, and 3.9 (IQR: 2-5) for transfer patients. Pulmonary function as measured by mean±SE of forced vital capacity percent predicted (FVC%p) was 94.5±0.8 for early ambulatory, 89.1±1.4 for late ambulatory, and 80.2±2.8 for transfer states, and decreased from 77.2±1.7 to 20.6±1.6 across the five non-ambulatory health states. In summary, these findings further characterize health states and their interpretation in economic modeling and decision-making in DMD management.

Cultural adaptation, validity and reliability of the Turkish version of north star ambulatory assessment.

The North Star Ambulatory Assessment (NSAA) is a functional motor outcome measure originally developed for patients with Duchenne muscular dystrophy (DMD). The aim of this study was to perform the cultural adaptation and investigate the validity and reliability of the Turkish version of the NSAA (T-NSAA) in DMD. After translation process, internal consistency, interrater and test-retest reliability of the NSAA were determined by using the Cronbach Alpha Coefficient and Intraclass Correlation Coefficient (ICC), respectively. Absolute reliability was determined by using the Standard Error of Measurement (SEM) with minimal detectable change at 95% limits of confidence (MDC95). Lower limb functionality of children was evaluated by Vignos Lower Extremity Scale (VLERS). To establish convergent validity, the correlations between T-NSAA and Motor Function Measure (MFM-32), 6-minute walk test (6-MWT), and VLERS were analyzed by using the Spearman's correlation coefficient. The study was completed with 86 patients with DMD whose age were mean 104.56 ± 24.66 months. The internal consistency (Cronbach's α = 0.94), intra-reliability (ICC = 0.977) and inter-reliability (ICC = 0.972) of T-NSAA were excellent. SEM and MDC values were low indicating satisfactory absolute agreement (< %10). The T-NSAA had strong correlations with the MFM-total score, 6-MWT, and VLERS (p < 0.01). T-NSAA is a valid and reliable tool to assess ambulatory status of Turkish-speaking DMD population. NCT05549999, Date of registration: September 19, 2022.

Advancing flourishing as the north star of medical education: A call for personal and professional development as key to becoming physicians

Over the past 15 years, multiple calls to transform medical education, and by extension, health sciences education, have addressed issues pertaining to learners’ subjective experiences as well as the learning environment. By and large, these calls to transform share many of the same themes: greater engagement with the humanities, enhanced professional identity formation, leadership development, as well as systemic changes to enhance meaning, purpose, and belonging. However, the many initiatives and reforms underway in medical education have yet to fully reach their desired outcomes – particularly those focused on enhancing meaning, purpose, and belonging. We suggest that calls to transform medical education can be unified and guided by focusing on the promotion of human flourishing. Briefly, we define human flourishing as an aspirational objective enabling one to reach a state of ‘wholeness—of being and doing, of realizing one’s potential and helping others do the same.’ We share our implications of a flourishing guided medical education journey for medical students, residents, and faculty.

AAV gene therapy for Duchenne muscular dystrophy: the EMBARK phase 3 randomized trial.

Duchenne muscular dystrophy (DMD) is a rare, X-linked neuromuscular disease caused by pathogenic variants in the DMD gene that result in the absence of functional dystrophin, beginning at birth and leading to progressive impaired motor function, loss of ambulation and life-threatening cardiorespiratory complications. Delandistrogene moxeparvovec, an adeno-associated rh74-viral vector-based gene therapy, addresses absent functional dystrophin in DMD. Here the phase 3 EMBARK study aimed to assess the efficacy and safety of delandistrogene moxeparvovec in patients with DMD. Ambulatory males with DMD, ≥4 years to <8 years of age, were randomized and stratified by age group and North Star Ambulatory Assessment (NSAA) score to single-administration intravenous delandistrogene moxeparvovec (1.33 × 1014 vector genomes per kilogram; n = 63) or placebo (n = 62). At week 52, the primary endpoint, change from baseline in NSAA score, was not met (least squares mean 2.57 (delandistrogene moxeparvovec) versus 1.92 (placebo) points; between-group difference, 0.65; 95% confidence interval (CI), -0.45, 1.74; P = 0.2441). Secondary efficacy endpoints included mean micro-dystrophin expression at week 12: 34.29% (treated) versus 0.00% (placebo). Other secondary efficacy endpoints at week 52 (between-group differences (95% CI)) included: Time to Rise (-0.64 (-1.06, -0.23)), 10-meter Walk/Run (-0.42 (-0.71, -0.13)), stride velocity 95th centile (0.10 (0.00, 0.19)), 100-meter Walk/Run (-3.29 (-8.28, 1.70)), time to ascend 4 steps (-0.36 (-0.71, -0.01)), PROMIS Mobility and Upper Extremity (0.05 (-0.08, 0.19); -0.04 (-0.24, 0.17)) and number of NSAA skills gained/improved (0.19 (-0.67, 1.06)). In total, 674 adverse events were recorded with delandistrogene moxeparvovec and 514 with placebo. There were no deaths, discontinuations or clinically significant complement-mediated adverse events; 7 patients (11.1%) experienced 10 treatment-related serious adverse events. Delandistrogene moxeparvovec did not lead to a significant improvement in NSAA score at week 52. Some of the secondary endpoints numerically favored treatment, although no statistical significance can be claimed. Safety was manageable and consistent with previous delandistrogene moxeparvovec trials. ClinicalTrials.gov: NCT05096221.

Orientation method based on lunar hour angle

Abstract Astronomical orientation is a crucial technique for obtaining high-precision azimuths. However, at night, this often relies on the North Star, which can be challenging to locate and identify. An orientation method is proposed based on the lunar hour angle as an alternative. By applying theories from astronomy and geodesy, we conduct an in-depth study of the key points and calculation steps for using a theodolite to measure the moon. By observing the moon’s edge and center and combining this with the observer’s geographic location and observation time, we calculate the lunar hour angle to determine the true north azimuth. To improve computational efficiency, an application has been developed to assist with observation and data processing. Practical applications and tests have validated the feasibility and effectiveness of this lunar hour angle-based orientation method. This method addresses the limitations of traditional North Star orientation, offering an efficient and convenient approach to orientation.

322P Rasch evaluation of North Star Ambulatory Assessment and North Star Assessment for limb-girdle type muscular dystrophies in Becker muscular dystrophy

322P Rasch evaluation of North Star Ambulatory Assessment and North Star Assessment for limb-girdle type muscular dystrophies in Becker muscular dystrophy

383P A qualitative evaluation of meaningful change on the north star ambulatory assessment and performance of upper limb in Duchenne muscular dystrophy

383P A qualitative evaluation of meaningful change on the north star ambulatory assessment and performance of upper limb in Duchenne muscular dystrophy

394P Longitudinal changes in the North Star Ambulatory Assessment and leg muscle fat fraction in DMD

394P Longitudinal changes in the North Star Ambulatory Assessment and leg muscle fat fraction in DMD

381P Survey results for use of the Performance of the Upper Limb Module in patients with Duchenne muscular dystrophy: UK North Star national registry

381P Survey results for use of the Performance of the Upper Limb Module in patients with Duchenne muscular dystrophy: UK North Star national registry

375P Relationship between Pediatric Outcomes Data Collection Instrument (PODCI) and North Star Ambulatory Assessment (NSAA)

375P Relationship between Pediatric Outcomes Data Collection Instrument (PODCI) and North Star Ambulatory Assessment (NSAA)

Efficacy and Safety of Vamorolone in Duchenne Muscular Dystrophy: A Systematic Review.

Vamorolone has recently been approved for the management of Duchenne muscular dystrophy to replace glucocorticosteroids, which theoretically have more side effects. However, its efficacy and safety profile is unclear. We aimed to assess the efficacy of vamorolone in Duchenne muscular dystrophy through the 6-minute walk test (6MWT), the North Star Ambulatory Assessment (NSAA), time to stand velocity (TTSTAND), time to run 10 m (TTRW), time to climb four stairs (TTCLIMB) and a safety profile. A systematic search was conducted in MEDLINE, Scopus, Web of Science and the Cochrane Library from inception to June 2024 (PROSPERO: CRD42024558413) for studies evaluating the effect or safety profile of vamorolone in a population with Duchenne muscular dystrophy on 6MWT, NSAA and TTSTAND. TTRW, TTCLIMB and a safety profile were included. The risk of bias was assessed using the Cochrane Collaboration's risk of bias tool (RoB2) and the Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group from the US National Institutes of Health National Heart, Lung, and Blood Institute, depending on the type of design. Results were expressed as mean differences or proportions with 95% confidence intervals (CIs), depending on the outcome. Six studies with a total of 145 individuals with Duchenne muscular dystrophy and a baseline age between 4.7 and 5.5 years were included in the systematic review. Overall, the most effective dose was 6 mg/kg/day. At 24 weeks, this dose showed a statistically significant effect compared with the untreated cohorts of 41.60 m (95% CI 14.30, 68.90) on the 6MWT, 3.57 points (95% CI 1.89, 5.25) on the NSAA, 0.06 events/s (95% CI 0.02, 0.10) on the TTSTAND, approximately 0.25 m/s on the TTRW and 0.04 (95% CI -0.00, 0.08) to 0.07 events/s (95% CI 0.03, 0.11) on the TTCLIMB. There was some discrepancy in the statistical significance of some studies, although the direction of the effect was usually similar. In general, the effect was maintained in the extension studies. Adverse events were less frequent than in historical cohorts treated with glucocorticoids. Finally, the risk of bias in the included studies was low. According to our results, vamorolone offers a statistically and clinically significant benefit in the management of Duchenne muscular dystrophy, with fewer side effects than glucocorticoids. However, the number of studies limits the interpretability and generalisability of these data, requiring more studies with more participants to perform a meta-analysis.

Skeletal muscle symptoms and quantitative MRI in females with dystrophinopathy.

The dystrophinopathies primarily affect males; however, female carriers of pathogenic dystrophin variants can develop skeletal muscle symptoms. This study aimed to evaluate muscle involvement and symptoms in females with dystrophinopathy using quantitative magnetic resonance imaging (MRI), functional assessments, and patient-reported outcomes. Controls and females with dystrophinopathy with muscle symptoms of pain, weakness, fatigue, or excessive tightness were enrolled in this cross-sectional study. Participants underwent lower extremity MRI to quantify muscle inflammation, replacement by fat, and disease asymmetry. Cardiac MRI, functional ability, muscle symptoms, and serum creatine kinase levels were also evaluated. Six pediatric females with dystrophinopathy (mean age: 11.7 years), 11 adult females with dystrophinopathy (mean age: 41.3 years), and seven controls enrolled. The mean fat fraction was increased in females with dystrophinopathy compared to controls in the soleus (0.11 vs. 0.03, p = .0272) and vastus lateralis (0.16 vs. 0.03, p = .004). Magnetic resonance spectroscopy water T2, indicative of muscle inflammation, was elevated in the soleus and/or vastus lateralis in 11 of 17 individuals. North Star Ambulatory Assessment score was lower in the dystrophinopathy group compared to controls (29 vs. 34 points, p = .0428). From cardiac MRI, left ventricle T1 relaxation times were elevated in females with dystrophinopathy compared to controls (1311 ± 55 vs. 1263 ± 25 ms, p < .05), but ejection fraction and circumferential strain did not differ. Symptomatic females with dystrophinopathy quantitatively demonstrate muscle replacement by fat and inflammation, along with impairments in functional ability and cardiac function. Additional research is needed to evaluate how symptoms and muscle involvement change longitudinally.

Understanding North Star Ambulatory Assessment total scores and their implications for standards of care using observational data

NorthStar Ambulatory Assessment (NSAA) total score (TS) is an ordinal scale to evaluate disease progression and treatment response in ambulatory Duchenne Muscular Dystrophy individuals. Clinical management according to standard of care could be enhanced by understanding how changes in the TS could inform standards of care. Here we describe the associated item performance patterns in the NorthStar Database for ranges of NSAA TS and its timed tests (10 metre walk/run and rise from floor ). We then compare these patterns depending on whether a participant is on an improving/stable (≤2-point loss in the prior year) or declining (>2-point loss in the prior year) trend. These TS and trends are subsequently linked and referenced to therapy standards of care. We included 761 participants from the UK NorthStar observational clinical database between 5-16 years, who were on steroids. Differences and trends in item ability, compensations, and times can suggest specific disease complications and lead towards anticipatory therapy recommendations. Families and therapists can benefit from using the TS and trend to guide therapy management.

Reductions in functional muscle mass and ability to ambulate in Duchenne muscular dystrophy from ages 4 to 24 years.

Duchenne muscular dystrophy (DMD) results in a progressive loss of functional skeletal muscle mass (MM) and replacement with fibrofatty tissue. Accurate evaluation of MM in DMD patients has not previously been available. Our objective was to measure MM using the D3creatine (D3Cr) dilution method and determine its relationship with strength and functional capacity in patients with DMD over a wide range of ages. Subjects were recruited for participation in a 12month, longitudinal, observational study. Here, we report the baseline data. A 20mg dose of D3Cr dissolved in water was ingested by 92 patients with DMD (ages 4-25years) followed later with a fasting urine sample. Enrichment of D3creatinine was determined by liquid chromatography-mass spectrometry analysis. The North Star Ambulatory Assessment (NSAA) total score was determined for ambulatory participants, and the Performance of Upper Limb (PUL 2.0) total score and grip strength for all participants. We observed a significant age-associated increase in body weight along with a substantial decrease in MM/body weight (%MM). MM and %MM were associated with PUL score (r=0.517, P<0.0001 and r=0.764, P<0.0001 respectively). The age-associated decrease in MM and %MM was strongly associated with ambulatory status. We observed very little overlap in %MM between ambulant and non-ambulant subjects, suggesting a threshold of 18-22% associated with loss of ambulation. MM is substantially diminished with advancing age and is highly related to clinically meaningful functional status. The D3Cr dilution method may provide a biomarker of disease progression and therapeutic efficacy in patients with DMD or other neuromuscular disorders. KEY POINTS: The non-invasive D3creatine dilution method provides novel data on whole body functional muscle mass (MM) in a wide range of ages in patients with DMD and reveals profoundly low functional MM in older non-ambulant patients. The difference in %MM between ambulant and non-ambulant subjects suggests a threshold for loss of ambulatory ability between 18 and 22% MM. The data suggest that as functional MM declines with age, maintaining a lower body weight may help to conserve ambulatory ability.

The Impact of Postural and Anthropometric Properties of Foot and Ankle on Physical Performance and Ambulation of Patients with Duchenne Muscular Dystrophy.

Abnormal foot anthropometry and posture of patients with Duchenne Muscular Dystrophy (DMD) can be considered as possible risk factors for performance and ambulation. It was aimed to examine the effects of foot posture and anthropometric characteristics, which deteriorated from the early period, on ambulation and performance of patients with DMD. The foot arch height (FAH), the metatarsal width (MW), subtalar pronation angle, and ankle limitation degree (ALD) were evaluated to determine the foot anthropometric characteristics of the patients. Foot Posture Index-6 (FPI-6) was used to evaluate foot posture. The performance of the patients was determined by the 6-minute walk test (6MWT), the 10-meter walk test (10MWT), and ascend/descend a standard 4-step test, and the ambulation was determined by the North Star Ambulatory Assessment (NSAA). Spearman's correlation coefficient was calculated to assess the relationship between foot anthropometric characteristics and posture, and performance and ambulation. The sample consisted of 48 patients with DMD aged 5.5 to 12 years. Both of the right and left foot FPI-6 scores were associated with all parameters, except descending 4-step. The left FAH was associated with 6MWT and NSAA, and the left MW was associated with 6MWT. The ALD of right foot was associated with 6MWT, ascending/descending 4 steps, and NSAA, and left ankle limitation was associated with NSAA (p<0.05). There was no relationship between other parameters. These findings suggest that postural disorders in the foot and ankle may contribute to the decrease in performance and ambulation in patients with DMD.

Large scale serum proteomics identifies proteins associated with performance decline and clinical milestones in Duchenne muscular dystrophy.

Serum biomarkers are promising minimally invasive outcome measures in clinical studies in Duchenne muscular dystrophy (DMD). However, biomarkers strongly associated with clinical progression and predicting performance decline are lacking. In this study we aimed to identify serum biomarkers associated with clinical performance and able to predict clinical milestones in DMD. Towards this aim we present a retrospective multi-center cohort study including serum samples and clinical data collected in research participants with DMD as part of a natural history study at the University of Florida (UF) and real-world observations at Leiden University Medical Center (LUMC) between 2009-2022. The 7K SomaScan® assay was used to analyse protein levels in in individual serum samples. Serum biomarkers predicted age at loss of ambulation (LoA), age at loss of overhead reach (OHR) and age at loss of hand to mouth function (HTM). Secondary outcomes were the association of biomarkers with age, corticosteroid (CS) usage, and clinical performance based on the North Star Ambulatory Assessment (NSAA), 10 meter run velocity (10mrv), 6 minute walk (6MWT) and Performance of the Upper Limb (PUL2.0). A total of 716 serum samples were collected in 79 participants at UF and 74 at LUMC (mean[SD] age; 10.9[3.2] vs 8.4[3.4]). 244 serum proteins showed an association with CS usage in both cohorts independent of CS type and regimen, including MMP3 and IGLL1. 318 probes (corresponding to 294 proteins) showed significant associations with NSAA, 10mrv, 6MWT and/or PUL2.0 across both cohorts. The expression of 38 probes corresponding to 36 proteins such as RGMA, EHMT2, ART3, ANTXR2 and DLK1 was associated with risk of both lower and upper limb clinical milestones in both the LUMC and UF cohort. In conclusion, multiple biomarkers were associated with CS use, motor function and upper lower and upper limb disease milestones in DMD. These biomarkers were validated across two independent cohorts, increasing their likelihood of translation for use within the broader DMD population.

"If you cannot measure it, you cannot improve it". Outcome measures in Duchenne Muscular Dystrophy: current and future perspectives.

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive neuromuscular disorder primarily affecting males, caused by mutations in the dystrophin gene. The absence of dystrophin protein leads to progressive skeletal muscle degeneration. Recent advances in the therapeutic landscape underscore the need to identify appropriate outcome measures to assess treatment efficacy in ambulant and non-ambulant DMD patients, across clinical and research settings. This is essential for accurately evaluating new treatments and attributing therapeutic benefits.It is crucial to establish a robust correlation between outcome scores and disease progression patterns. This task is challenging since functional test performance may be influenced by different patient's characteristics, including the physiological evolution of the neurodevelopment together with the disease progression. While widely used DMD outcomes such as the North Star Ambulatory Assessment, the 6-Minute Walking Test, the 4 stairs climbed, and the Performance of the Upper Limb exhibit reliability and validity, their clinical significance is influenced by the wide phenotype and progression variability of the disease.We present and discuss the features (relevance, quantifiability, validity, objectivity, reliability, sensitivity, specificity, precision) of available DMD outcome measures, including new potential measures that may be provided by digital tools and artificial intelligence.