Artificial Intelligence-Based Digital Biomarkers for Type 2 Diabetes: A Review.

Type 2 diabetes mellitus (T2DM), a complex metabolic disorder that burdens the health care system, requires early detection and treatment. Recent strides in digital health technologies, coupled with artificial intelligence (AI), may have the potential to revolutionize T2DM screening, diagnosis of complications, and management through the development of digital biomarkers. This review provides an overview of the potential applications of AI-driven biomarkers in the context of screening, diagnosing complications, and managing patients with T2DM. The benefits of using multisensor devices to develop digital biomarkers are discussed. The summary of these findings and patterns between model architecture and sensor type are presented. In addition, we highlight the pivotal role of AI techniques in clinical intervention and implementation, encompassing clinical decision support systems, telemedicine interventions, and population health initiatives. Challenges such as data privacy, algorithm interpretability, and regulatory considerations are also highlighted, alongside future research directions to explore the use of AI-driven digital biomarkers in T2DM screening and management.

USP53 Regulates Bone Homeostasis by Controlling Rankl Expression in Osteoblasts and Bone Marrow Adipocytes.

In the skeleton, osteoblasts and osteoclasts synchronize their activities to maintain bone homeostasis and integrity. Investigating the molecular mechanisms governing bone remodeling is critical and helps understand the underlying biology of bone disorders. Initially, we have identified the ubiquitin-specific peptidase gene (Usp53) as a target of the parathyroid hormone in osteoblasts and a regulator of mesenchymal stem cell differentiation. Mutations in USP53 have been linked to a constellation of developmental pathologies. However, the role of Usp53 in bone has never been visited. Here we show that Usp53 null mice have a low bone mass phenotype in vivo. Usp53 null mice exhibit a pronounced decrease in trabecular bone indices including trabecular bone volume (36%) and trabecular number (26%) along with an increase in trabecular separation (13%). Cortical bone parameters are also impacted, showing a reduction in cortical bone volume (12%) and cortical bone thickness (15%). As a result, the strength and mechanical bone properties of Usp53 null mice have been compromised. At the cellular level, the ablation of Usp53 perturbs bone remodeling, augments osteoblast-dependent osteoclastogenesis, and increases osteoclast numbers. Bone marrow adipose tissue volume increased significantly with age in Usp53-deficient mice. Usp53 null mice displayed increased serum receptor activator of NF-κB ligand (RANKL) levels, and Usp53-deficient osteoblasts and bone marrow adipocytes have increased expression of Rankl. Mechanistically, USP53 regulates Rankl expression by enhancing the interaction between VDR and SMAD3. This is the first report describing the function of Usp53 during skeletal development. Our results put Usp53 in display as a novel regulator of osteoblast-osteoclast coupling and open the door for investigating the involvement of USP53 in pathologies. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Vibration Measurements of the Gerbil Eardrum Under Quasi-static Pressure Sweeps.

Tympanometry provides an objective measurement of the status of the middle ear. During tympanometry, the ear-canal pressure is varied, while the response of the ear to sound pressure is measured. The effects of the pressure on the mechanics of the middle ear are not well understood. This study is a continuation of our previous work in which the vibration response of the gerbil eardrum was measured in vivo under quasi-static pressure steps. In this study, we delivered a continuous pressure sweep to the middle ear and measured the vibration response at four locations for six gerbils. Vibrations were recorded using a single-point laser Doppler vibrometer and glass-coated reflective beads (diameter ~ 40 µm) at the umbo and on the mid-manubrium, posterior pars tensa and anterior pars tensa.The vibration magnitudes were similar to those in the previous step-wise pressurization experiments. Most gerbils showed repeatability within less than 10 dB for consecutive cycles. As described in the previous study, as the frequency was increased at ambient pressure, the vibration magnitude on the manubrium increased slightly to a broad peak (referred to as R1) and then decreased until a small peak appeared (referred to as R2), followed by multiple peaks and troughs as the magnitude decreased further. The low-frequency vibration magnitude (at 1 kHz) decreased monotonically as the pressure became more negative except for a dip (about 500 Pa wide) that occurred between - 700 and - 1800 Pa. The lowest overall magnitude was recorded in the dip at mid-manubrium. The vibration magnitudes also decreased as the middle-ear pressure was made more positive and were larger than those at negative pressures. R1 was only visible at negative and small positive middle-ear pressures, while R2 was visible for both positive and negative pressures. R2 split into multiple branches after the middle-ear pressure became slightly positive. No magnitude dip was visible for positive middle-ear pressures.The low-frequency vibration magnitudes at negative middle-ear pressures on the pars tensa were higher than those on the manubrium. R1 was not visible for large negative middle-ear pressures on the pars tensa. R2 appeared as a multi-peak feature on the pars tensa as well, and a higher-frequency branch on the posterior pars tensa appeared as a trough on the anterior pars tensa. The magnitude dip was not present on the pars tensa. The largest overall magnitude was recorded at the R2 peak on the posterior pars tensa.The results of this study expand on the findings of the step-wise pressurization experiments and provide further insight into the evolution of the vibration response of the eardrum under quasi-static pressures.

Vibration Measurements of the Gerbil Eardrum Under Quasi-static Pressure Steps.

Tympanometry is a relatively simple non-invasive test of the status of the middle ear. An important step towards understanding the mechanics of the middle ear during tympanometry is to make vibration measurements on the eardrum under tympanometric pressures. In this study, we measured in vivo vibration responses in 11 gerbils while varying the middle-ear pressure quasi-statically, with the ear canal at ambient pressure. Vibrations were recorded using a single-point laser Doppler vibrometer with five glass-coated reflective beads (diameter ~ 40 µm) as targets. The locations were the umbo, mid-manubrium, posterior pars tensa, anterior pars tensa and pars flaccida. As described in earlier studies, the unpressurized vibration magnitude was flat at low frequencies, increased until a resonance frequency at around 1.8-2.5 kHz, and became complex at higher frequencies. At both the umbo and mid-manubrium points, when the static pressure was decreased to the most negative middle-ear pressure (- 2500 Pa), the low-frequency vibration magnitude (measured at 1.0 kHz) showed a monotonic decrease, except for an unexpected dip at around - 500 to - 1000 Pa. This dip was not present for the pars-tensa and pars-flaccida points. The resonance frequency shifted to higher frequencies, to around 7-8 kHz at - 2500 Pa. For positive middle-ear pressures, the low-frequency vibration magnitude decreased monotonically, with no dip, and the resonance frequency shifted to around 5-6 kHz at + 2500 Pa. There was more inter-specimen variability on the positive-pressure side than on the negative-pressure side. The low-frequency vibration magnitudes on the negative-pressure side were higher for the pars-tensa points than for the umbo and mid-manubrium points, while the magnitudes were similar at all four locations on the positive-pressure side. Most gerbils showed repeatability within less than 10 dB for consecutive cycles. The results of this study provide insight into the mechanics of the gerbil middle ear under tympanometric pressures.