Fair and equitable AI in biomedical research and healthcare: Social science perspectives.

Artificial intelligence (AI) offers opportunities but also challenges for biomedical research and healthcare. This position paper shares the results of the international conference "Fair medicine and AI" (online 3-5 March 2021). Scholars from science and technology studies (STS), gender studies, and ethics of science and technology formulated opportunities, challenges, and research and development desiderata for AI in healthcare. AI systems and solutions, which are being rapidly developed and applied, may have undesirable and unintended consequences including the risk of perpetuating health inequalities for marginalized groups. Socially robust development and implications of AI in healthcare require urgent investigation. There is a particular dearth of studies in human-AI interaction and how this may best be configured to dependably deliver safe, effective and equitable healthcare. To address these challenges, we need to establish diverse and interdisciplinary teams equipped to develop and apply medical AI in a fair, accountable and transparent manner. We formulate the importance of including social science perspectives in the development of intersectionally beneficent and equitable AI for biomedical research and healthcare, in part by strengthening AI health evaluation.

Safety and effectiveness of hyaluronic acid dermal filler in correction of moderate-to-severe nasolabial folds in Chinese subjects.

BACKGROUND: Modified sodium hyaluronate gel for injection, Princess® VOLUME (PV), has been on the European market since 2009 to correct deeper wrinkles and folds, increasing or restoring volume of the face, and remodeling facial contours. OBJECTIVE: To evaluate the safety and effectiveness of PV in correction of moderate-to-severe nasolabial folds (NLF) in Chinese subjects. METHODS: In this prospective, split-face, randomized, evaluator and subject-blinded, multicenter, noninferiority trial, 120 subjects were randomized to bilateral NLF treatment with PV administered in one NLF and Restylane® (RL) administered in the other NLF. NLFs were evaluated using the validated 5-point Wrinkle Severity Rating Scale with scores ranging from 1= none (no visible NLF) to 5= very severe (extremely deep and long NLF). Response was defined as ≥1 point improvement at Week 24 assessed by the blinded independent review committee (IRC) and the reduction of NLF severity, assessed by subjects and IRC based on the Global Aesthetic Improvement Scale. RESULTS: Among the 115 subjects who completed the study, median initial and touch-up volumes (mL) were 1.00 for both groups with a maximum dosage per NLF of 2.00 and a minimum of 0.30 for PV and 0.60 for RL. At week 24, the Wrinkle Severity Rating Scale improvement rate, as assessed by the IRC, reached 68.70% for PV and 52.17% for RL. The results indicate that PV is noninferior to RL (p<0.001). Most frequently reported adverse events for both devices were injection site swelling and procedural pain. The severity of the majority of the adverse events was mild. CONCLUSION: This study confirms that PV is a safe and effective treatment for the correction of moderate-to-severe NLFs in Chinese subjects.

A Controlled, Randomized Double-Blind Study to Evaluate the Safety and Efficacy of Chitosan-N-Acetylcysteine for the Treatment of Dry Eye Syndrome.

PURPOSE: This study was designed to evaluate the effect of chitosan-N-acetylcysteine (C-NAC) eye drops on tear film thickness (TFT) in patients with dry eye syndrome (DES). METHODS: This was a controlled, randomized, double-blind clinical investigation with patients assigned to 2 cohorts. In Cohort I, 21 patients were randomized to receive 1 instillation of C-NAC eye drops in 1 eye and placebo (normal saline solution) in the contralateral eye. In Cohort II, 17 patients were randomized to receive C-NAC eye drops once (QD) or twice (BID) daily for 5 days. TFT was assessed with a custom-built ultrahigh-resolution optical coherence tomography system. RESULTS: In Cohort I, mean TFT increased from 3.9 ± 0.5 µm predose to 4.8 ± 1.1 µm 10 min postdose after treatment with C-NAC. The increase was significantly different from placebo over time (P < 0.0001) and remained stable until 24 h postdose. In Cohort II, TFT increased with QD and BID instillation, with no significant difference between regimens. In both groups, Ocular Surface Disease Index scores improved, fewer patients presented with corneal damage, and symptoms of ocular discomfort/conjunctival redness were reduced. CONCLUSIONS: A single instillation of C-NAC significantly increased mean TFT in patients with DES as early as 10 min after instillation and lasted for 24 h. The magnitude of the increase in TFT following a single instillation was comparable with that after instillation twice daily over 5 days. Corneal damage improved in >60% of patients. C-NAC could be a viable treatment option for DES.

A Novel Cross-Linked Hyaluronic Acid Porous Scaffold for Cartilage Repair: An In Vitro Study With Osteoarthritic Chondrocytes.

PURPOSE: An important feature of biomaterials used in cartilage regeneration is their influence on the establishment and stabilization of a chondrocytic phenotype of embedded cells. The purpose of this study was to examine the effects of a porous 3-dimensional scaffold made of cross-linked hyaluronic acid on the expression and synthesis performance of human articular chondrocytes. MATERIALS AND METHODS: Osteoarthritic chondrocytes from 5 patients with a mean age of 74 years were passaged twice and cultured within the cross-linked hyaluronic acid scaffolds for 2 weeks. Analyses were performed at 3 different time points. For estimation of cell content within the scaffold, DNA-content (CyQuant cell proliferation assay) was determined. The expression of chondrocyte-specific genes by embedded cells as well as the total amount of sulfated glycosaminoglycans produced during the culture period was analyzed in order to characterize the synthesis performance and differentiation status of the cells. RESULTS: Cells showed a homogenous distribution within the scaffold. DNA quantification revealed a reduction of the cell number. This might be attributed to loss of cells from the scaffold during media exchange connected with a stop in cell proliferation. Indeed, the expression of cartilage-specific genes and the production of sulfated glycosaminoglycans were increased and the differentiation index was clearly improved. CONCLUSIONS: These results suggest that the attachment of osteoarthritic P2 chondrocytes to the investigated material enhanced the chondrogenic phenotype as well as promoted the retention.

An open-label uncontrolled, multicenter study for the evaluation of the efficacy and safety of the dermal filler Princess VOLUME in the treatment of nasolabial folds.

The dermal filler Princess VOLUME is a highly cross-linked, viscoelastic hyaluronic acid injectable gel implant used for aesthetic treatment. To evaluate the efficacy and safety of Princess VOLUME in the treatment of nasolabial folds, an open-label uncontrolled, multicenter study was conducted. Forty-eight subjects were recruited who had moderate to deep wrinkles, according to the Modified Fitzpatrick Wrinkle Scale (MFWS). Subjects received Princess VOLUME in both nasolabial folds at Day 0. Nasolabial fold severity was evaluated at 30, 90, 180, and 270 days after treatment, using the MFWS and the Global Aesthetic Improvement Scale (GAIS). Adverse events and treatment site reactions were recorded. Among the 48 subjects, 93.8% were female with a median age of 52 years. There were significant improvements (P < 0.0001) in the MFWS scores at 30, 180, and 270 days after treatment compared with those at baseline, with a mean decrease of 1.484 (±0.408), 1.309 (±0.373), and 1.223 (±0.401), respectively; hence the primary endpoint was achieved and clinical efficacy demonstrated. Princess VOLUME was well tolerated, and most adverse events were injection site reactions of mild to moderate severity. Subject satisfaction (97.9%), subject recommendation of the treatment (93.6%), and investigators GAIS scores (97.9% improvement) were high.

Bioguided isolation of (9Z)-octadec-9-enoic acid from Phellodendron amurense Rupr. and identification of fatty acids as PTP1B inhibitors.

The therapy of type-2 diabetes mellitus is one of the major challenges of our age. A possible strategy to prevent the progression of this disease is the inhibition of protein tyrosine phosphatase 1B (PTP1B), a major negative regulator in the insulin and leptin signalling pathway. Phellodendri amurensis cortex is a well-known Asian herbal drug traditionally used as antiphlogistic, antibacterial, and anti-inflammatory agent, and its efficacy against diabetes-related symptoms is reported as well. However, information regarding active principle(s) or the molecular mode of action was scarce. By bioguided isolation using an IN VITRO enzyme assay with human recombinant PTP1B, (9 Z)-octadec-9-enoic acid (oleic acid) could be identified as a major PTP1B inhibitor in the bark of Phellodendron amurENSE Rupr. (Rutaceae); it showed an IC50 value of 6.2 µM. Consistent with this inhibition of PTP1B, oleic acid was capable of enhancing insulin signalling in wild-type, but not PTP1B knockout fibroblasts. By testing a series of other fatty acids of different chain length and degree of saturation, their general PTP1B-inhibitory potential in the micromolar range was observed. More pronounced effects were associated with a longer carbon backbone and saturation of the double bonds. Therefore, our work provides first scientific evidences for the antidiabetic properties of P. amurense via a new target, effects which seem to be explainable by oleic acid. The discovery of a PTP1B inhibition by many fatty acids also adds a novel facet to the pharmacological properties of a class of compounds that is found in many food items in considerable amount and triggers speculation over their possible involvement in the feedback regulation of cellular fatty acid synthesis.

Bioactivity-guided isolation of 1,2,3,4,6-Penta-O-galloyl-D-glucopyranose from Paeonia lactiflora roots as a PTP1B inhibitor.

The inhibition of protein tyrosine phosphatase 1B (PTP1B) is of substantial interest for the treatment of type-2 diabetes mellitus. Using an in vitro enzyme assay with human recombinant PTP1B 1,2,3,4,6-penta-O-galloyl-D-glucopyranose was isolated from the roots of Paeonia lactiflora as an inhibitor of PTP1B, with an IC(50) value of 4.8 µM. Additionally, 1 was shown to act as an insulin sensitizer in human hepatoma cells (HCC-1.2) at a concentration of 10 µM. Thus, a potential new mechanism of action is provided explaining the antidiabetic properties of P. lactiflora.