Structural And Mechanical Responses To Intermittent Parathyroid Hormone Treatment, Discontinuation And Cyclic Administration Regimens

Bone mineral density rapidly decreases upon withdrawal from intermittent parathyroid hormone (PTH) treatment despite its potent effect of promoting bone formation. To better understand this adverse phenomenon, this study first aimed to investigate the phenotype of PTH withdrawal in both intact and estrogen-deficient rat model by using a well-designed experiment combined with innovative longitudinal imaging techniques and localized cellular activities. Due to observing a continuous anabolic window upon early discontinuation of PTH treatment in estrogen-deficient animals, we propose a potential effective treatment strategy, the short cycles of PTH and antiresorptive treatment regimen, which could extend the anabolic windows by increasing the number of newly activated modeling-based bone formation (MBF) sites. Lastly, to understand the structure-function relationships of bone tissue formed through MBF compared to the remodeling-based bone formation (RBF), we developed an innovative imaging platform with a mechanical testing platform to determine the mechanical properties of MBF and RBF and their long-term contributions in intact animals

A Flexible-Frame-Rate Vision-Aided Inertial Object Tracking System for Mobile Devices

Real-time object pose estimation and tracking is challenging but essential for emerging augmented reality (AR) applications. In general, state-of-the-art methods address this problem using deep neural networks which indeed yield satisfactory results. Nevertheless, the high computational cost of these methods makes them unsuitable for mobile devices where real-world applications usually take place. In addition, head-mounted displays such as AR glasses require at least 90~FPS to avoid motion sickness, which further complicates the problem. We propose a flexible-frame-rate object pose estimation and tracking system for mobile devices. It is a monocular visual-inertial-based system with a client-server architecture. Inertial measurement unit (IMU) pose propagation is performed on the client side for high speed tracking, and RGB image-based 3D pose estimation is performed on the server side to obtain accurate poses, after which the pose is sent to the client side for visual-inertial fusion, where we propose a bias self-correction mechanism to reduce drift. We also propose a pose inspection algorithm to detect tracking failures and incorrect pose estimation. Connected by high-speed networking, our system supports flexible frame rates up to 120 FPS and guarantees high precision and real-time tracking on low-end devices. Both simulations and real world experiments show that our method achieves accurate and robust object tracking

r-Hint: A message-efficient random access response for mMTC in 5G networks

Massive Machine Type Communication (mMTC) has attracted increasing attention due to the explosive growth of IoT devices. Random Access (RA) for a large number of mMTC devices is especially difficult since the high signaling overhead between User Equipments (UEs) and an eNB may overwhelm the available spectrum resources. To address this issue, we propose “respond by hint” (r-Hint), an ID-free handshaking protocol for contention-based RA in mMTC. The core idea of r-Hint is to avoid sequentially notifying contending UEs of their IDs by broadcasting a hint in the RA Response (RAR). To do so, we exploit the concept of prime factorization and hashing to encode the hint such that UEs can extract their required information accordingly. Our simulation results show that r-Hint reduces the RAR message size by 20%–40%. Such reduction can be translated to around 50% improvement of spectrum efficiency in LTE-M

Abaloparatide Maintains Normal Rat Blood Calcium Level in Part Via 1,25-Dihydroxyvitamin D/osteocalcin Signaling Pathway

The PTH-related peptide(1-34) analog, abaloparatide (ABL), is the second anabolic drug available for the treatment of osteoporosis. Previous research demonstrated that ABL had a potent anabolic effect but caused hypercalcemia at a significantly lower rate. However, the mechanism by which ABL maintains the stability of blood calcium levels remains poorly understood. Our in vivo data showed that ABL treatment (40 µg/kg/day for 7 days) significantly increased rat blood level of 1,25-dihydroxyvitamin D [1,25-(OH)2D] without raising the blood calcium value. ABL also significantly augmented the carboxylated osteocalcin (Gla-Ocn) in the blood and bone that is synthesized by osteoblasts, and increased noncarboxylated Ocn, which is released from the bone matrix to the circulation because of osteoclast activation. The in vitro data showed that ABL (10 nM for 24 hours) had little direct effects on 1,25-(OH)2D synthesis and Gla-Ocn formation in nonrenal cells (rat osteoblast-like cells). However, ABL significantly promoted both 1,25-(OH)2D and Gla-Ocn formation when 25-hydroxyvitamin D, the substrate of 1α-hydroxylase, was added to the cells. Thus, the increased 1,25-(OH)2D levels in rats treated by ABL result in high levels of Gla-Ocn and transient calcium increase in the circulation. Gla-Ocn then mediates calcium ions in the extracellular fluid at bone sites to bind to hydroxyapatite at bone surfaces. This regulation by Gla-Ocn at least, in part, maintains the stability of blood calcium levels during ABL treatment. We conclude that the signaling pathway of ABL/1,25-(OH)2D/Gla-Ocn contributes to calcium homeostasis and may help understand the mechanism of ABL for osteoporosis therapy

Self-supervised learning-based general laboratory progress pretrained model for cardiovascular event detection

The inherent nature of patient data poses several challenges. Prevalent cases amass substantial longitudinal data owing to their patient volume and consistent follow-ups, however, longitudinal laboratory data are renowned for their irregularity, temporality, absenteeism, and sparsity; In contrast, recruitment for rare or specific cases is often constrained due to their limited patient size and episodic observations. This study employed self-supervised learning (SSL) to pretrain a generalized laboratory progress (GLP) model that captures the overall progression of six common laboratory markers in prevalent cardiovascular cases, with the intention of transferring this knowledge to aid in the detection of specific cardiovascular event. GLP implemented a two-stage training approach, leveraging the information embedded within interpolated data and amplify the performance of SSL. After GLP pretraining, it is transferred for TVR detection. The proposed two-stage training improved the performance of pure SSL, and the transferability of GLP exhibited distinctiveness. After GLP processing, the classification exhibited a notable enhancement, with averaged accuracy rising from 0.63 to 0.90. All evaluated metrics demonstrated substantial superiority (p < 0.01) compared to prior GLP processing. Our study effectively engages in translational engineering by transferring patient progression of cardiovascular laboratory parameters from one patient group to another, transcending the limitations of data availability. The transferability of disease progression optimized the strategies of examinations and treatments, and improves patient prognosis while using commonly available laboratory parameters. The potential for expanding this approach to encompass other diseases holds great promise.Comment: published in IEEE Journal of Translational Engineering in Health & Medicin

Real-time Automatic M-mode Echocardiography Measurement with Panel Attention from Local-to-Global Pixels

Motion mode (M-mode) recording is an essential part of echocardiography to measure cardiac dimension and function. However, the current diagnosis cannot build an automatic scheme, as there are three fundamental obstructs: Firstly, there is no open dataset available to build the automation for ensuring constant results and bridging M-mode echocardiography with real-time instance segmentation (RIS); Secondly, the examination is involving the time-consuming manual labelling upon M-mode echocardiograms; Thirdly, as objects in echocardiograms occupy a significant portion of pixels, the limited receptive field in existing backbones (e.g., ResNet) composed from multiple convolution layers are inefficient to cover the period of a valve movement. Existing non-local attentions (NL) compromise being unable real-time with a high computation overhead or losing information from a simplified version of the non-local block. Therefore, we proposed RAMEM, a real-time automatic M-mode echocardiography measurement scheme, contributes three aspects to answer the problems: 1) provide MEIS, a dataset of M-mode echocardiograms for instance segmentation, to enable consistent results and support the development of an automatic scheme; 2) propose panel attention, local-to-global efficient attention by pixel-unshuffling, embedding with updated UPANets V2 in a RIS scheme toward big object detection with global receptive field; 3) develop and implement AMEM, an efficient algorithm of automatic M-mode echocardiography measurement enabling fast and accurate automatic labelling among diagnosis. The experimental results show that RAMEM surpasses existing RIS backbones (with non-local attention) in PASCAL 2012 SBD and human performances in real-time MEIS tested. The code of MEIS and dataset are available at https://github.com/hanktseng131415go/RAME

Gradient static-strain stimulation in a microfluidic chip for 3D cellular alignment

This is the published version. Copyright 2014 Royal Society of ChemistryCell alignment is a critical factor to govern cellular behavior and function for various tissue engineering applications ranging from cardiac to neural regeneration. In addition to physical geometry, strain is a crucial parameter to manipulate cellular alignment for functional tissue formation. In this paper, we introduce a simple approach to generate a range of gradient static strains without external mechanical control for the stimulation of cellular behavior within 3D biomimetic hydrogel microenvironments. A glass-supported microfluidic chip with a convex flexible polydimethylsiloxane (PDMS) membrane on the top was employed for loading the cells suspended in a prepolymer solution. Following UV crosslinking through a photomask with a concentric circular pattern, the cell-laden hydrogels were formed in a height gradient from the center (maximum) to the boundary (minimum). When the convex PDMS membrane retracted back to a flat surface, it applied compressive gradient forces on the cell-laden hydrogels. The concentric circular hydrogel patterns confined the direction of hydrogel elongation, and the compressive strain on the hydrogel therefore resulted in elongation stretch in the radial direction to guide cell alignment. NIH3T3 cells were cultured in the chip for 3 days with compressive strains that varied from ~65% (center) to ~15% (boundary) on hydrogels. We found that the hydrogel geometry dominated the cell alignment near the outside boundary, where cells aligned along the circular direction, and the compressive strain dominated the cell alignment near the center, where cells aligned radially. This study developed a new and simple approach to facilitate cellular alignment based on hydrogel geometry and strain stimulation for tissue engineering applications. This platform offers unique advantages and is significantly different from the existing approaches owing to the fact that gradient generation was accomplished in a miniature device without using an external mechanical source

Micro-Computed Tomographic Analysis of the Shaping Ability of XP-Endo Shaper in Oval-Shaped Distal Root Canals of Mandibular Molars

Objective: To compare the shaping ability of the XP-endo Shaper (XPS) system to the ProTaper Next (PTN) system in oval-shaped distal root canals. Methods: From 12 mandibular molars, distal roots with moderately curved single oval canals were randomly assorted to be instrumented with XPS (experimental group) or PTN (control group) and then scanned using micro-computed tomography [Scan 1]. The root canals of the XPS samples were prepared following the manufacturer\u27s instructions using 15 insertions (XPS15) and rescanned [Scan 2]. An additional 10 insertions to the working length were applied, totalling 25 insertions (XPS25), and the roots were rescanned again [Scan 3]. PTN samples were prepared up to the X3 instrument (PTNX3) and rescanned [Scan 2]. The dentine removed and the unprepared areas were assessed. Data were analysed using a t-test with significance at α=0.05. Results: XPS25 was associated with a significantly greater dentine removal than XPS15 over the entire root canal length and in all three-thirds of the root canal (P\u3c0.05). XPS25 significantly removed more dentine than PTNX3 in only the coronal third (P\u3c0.05). XPS25 was also associated with a significantly smaller percentage of unprepared areas than XPS15 overall and in the coronal third (P\u3c0.05). PTNX3 was associated with a significantly larger percentage of unprepared areas than XPS15 and XPS25 overall and in the coronal and middle thirds (P\u3c0.05). Conclusion: Ten additional movements with XPS significantly improved instrumentation capacity, reducing the percentage of untouched surface areas but also removing more dentine

Pathophysiology of Neuropathic Pain in Type 2 Diabetes: Skin denervation and contact heat–evoked potentials

OBJECTIVE: Neuropathic pain due to small-fiber sensory neuropathy in type 2 diabetes can be diagnosed by skin biopsy with quantification of intra- epidermal nerve fiber ( IENF) density. There is, however, a lack of noninvasive physiological assessment. Contact heat-evoked potential ( CHEP ) is a newly developed approach to record cerebral responses of A fiber- mediated thermonociceptive stimuli. We investigated the diagnostic role of CHEP. RESEARCH DESIGN AND METHODS: From 2006 to 2009, there were 32 type 2 diabetic patients (20 males and 12 females, aged 51.63 10.93 years) with skin denervation and neuropathic pain. CHEPs were recorded with heat stimulations at the distal leg, where skin biopsy was performed. RESULTS: CHEP amplitude was reduced in patients compared with age- and sex-matched control subjects (14.8 15.6 vs. 33.7 10.1 V, P < 0.001). Abnormal CHEP patterns ( reduced amplitude or prolonged latency) were noted in 81.3 % of these patients. The CHEP amplitude was the most significant parameter correlated with IENF density (P = 0. 003) and pain perception to contact heat stimuli (P = 0.019) on multiple linear regression models. An excitability index was derived by calculating the ratio of the CHEP amplitude over the IENF density. This excitability index was higher in diabetic patients than in control subjects (P = 0.023), indicating enhanced brain activities in neuropathic pain. Among different neuropathic pain symptoms, the subgroup with evoked pain had higher CHEP amplitudes than the subgroup without evoked pain (P = 0.011). CONCLUSIONS: CHEP offers a noninvasive approach to evaluate the degeneration of thermonociceptive nerves in diabetic neuropathy by providing physiological correlates of skin denervation and neuropathic pain