2,125 research outputs found
A Large-Scale Feasibility Study of Screen-based 3D Visualization and Augmented Reality Tools for Human Anatomy Education: Exploring Gender Perspectives in Learning Experience
Anatomy education is an indispensable part of medical training, but
traditional methods face challenges like limited resources for dissection in
large classes and difficulties understanding 2D anatomy in textbooks. Advanced
technologies, such as 3D visualization and augmented reality (AR), are
transforming anatomy learning. This paper presents two in-house solutions that
use handheld tablets or screen-based AR to visualize 3D anatomy models with
informative labels and in-situ visualizations of the muscle anatomy. To assess
these tools, a user study of muscle anatomy education involved 236 premedical
students in dyadic teams, with results showing that the tablet-based 3D
visualization and screen-based AR tools led to significantly higher learning
experience scores than traditional textbook. While knowledge retention didn't
differ significantly, ethnographic and gender analysis showed that male
students generally reported more positive learning experiences than female
students. This study discusses the implications for anatomy and medical
education, highlighting the potential of these innovative learning tools
considering gender and team dynamics in body painting anatomy learning
interventions.Comment: This work is accepted and presented at IEEE International Conference
on Artificial Intelligence & extended and Virtual Reality (AIxVR 2024
Inhibition of the Gab2/PI3K/mTOR signaling ameliorates myeloid malignancy caused by Ptpn11 (Shp2) gain-of-function mutations
Activating mutations, such as E76K and D61Y, in PTPN11 (SHP2), a protein tyrosine phosphatase implicated in multiple cell signaling processes, are associated with 35% of patients with juvenile myelomonocytic leukemia (JMML), an aggressive childhood myeloproliferative neoplasm (MPN). Here we show that the interaction between leukemia-associated mutant Shp2 and Gab2, a scaffolding protein important for cytokine-induced PI3K/Akt signaling, was enhanced, and that the mTOR pathway was elevated in Ptpn11E76K/+ leukemic cells. Importantly, MPN induced by the Ptpn11E76K/+ mutation was markedly attenuated in Ptpn11E76K/+/Gab2-/- double mutant mice-overproduction of myeloid cells was alleviated, splenomegaly was diminished and myeloid cell infiltration in nonhematopoietic organs was decreased in these double mutants. Excessive myeloid differentiation of stem cells was also normalized by depletion of Gab2. Acute leukemia progression of MPN was reduced in the double mutant mice and, as such, their survival was much prolonged. Furthermore, treatment of Ptpn11E76K/+ mice with Rapamycin, a specific and potent mTOR inhibitor, mitigated MPN phenotypes. Collectively, this study reveals an important role of the Gab2/PI3K/mTOR pathway in mediating the pathogenic signaling of the PTPN11 gain-of-function mutations and a therapeutic potential of Rapamycin for PTPN11 mutation-associated JMML
Therapeutic Potential of Targeting the Oncogenic SHP2 Phosphatase
, The Src homology 2 domain containing
protein tyrosine phosphatase-2
(SHP2) is an oncogenic phosphatase associated with various kinds of
leukemia and solid tumors. Thus, there is substantial interest in
developing SHP2 inhibitors as potential anticancer and antileukemia
agents. Using a structure-guided and fragment-based library approach,
we identified a novel hydroxyindole carboxylic acid-based SHP2 inhibitor 11a-1, with an IC50 value of 200 nM
and greater than 5-fold selectivity against 20 mammalian PTPs. Structural
and modeling studies reveal that the hydroxyindole carboxylic acid
anchors the inhibitor to the SHP2 active site, while interactions
of the oxalamide linker and the phenylthiophene tail with residues
in the β5–β6 loop contribute
to 11a-1’s binding potency and selectivity.
Evidence suggests that 11a-1 specifically
attenuates the SHP2-dependent signaling inside the cell. Moreover, 11a-1 blocks growth factor mediated Erk1/2 and
Akt activation and exhibits excellent antiproliferative activity in
lung cancer and breast cancer as well as leukemia cell lines
Tumor glucose metabolism imaged in vivo in small animals with whole-body photoacoustic computed tomography
With the increasing use of small animals for human disease studies, small-animal whole-body molecular imaging plays an important role in biomedical research. Currently, none of the existing imaging modalities can provide both anatomical and glucose molecular information, leading to higher costs of building dual-modality systems. Even with image co-registration, the spatial resolution of the molecular imaging modality is not improved. Utilizing a ring-shaped confocal photoacoustic computed tomography system, we demonstrate, for the first time, that both anatomy and glucose uptake can be imaged in a single modality. Anatomy was imaged with the endogenous hemoglobin contrast, and glucose metabolism was imaged with a near-infrared dye-labeled 2-deoxyglucose
Modeling biological age using blood biomarkers and physical measurements in Chinese adults
Background This study aimed to: 1) assess the associations of biological age acceleration based on Klemera and Doubal's method (KDM-AA) with long-term risk of all-cause mortality; and 2) compare the association of KDM-AA with all-cause mortality among participants potentially at different stages of the cardiovascular disease (CVD) continuum.
Methods The present study was based on a subpopulation of the China Kadoorie Biobank, with baseline survey during 2004–08. A total of 12,377 participants free of ischemic heart disease, stroke, or cancer at baseline were included, in which 8180 participants were identified to develop major coronary event (MCE), ischemic stroke (IS), intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH), and 4197 remained free of these cardiovascular diseases before 1 January 2014. These participants were followed up until 1 Jan 2018. KDM-AA was calculated by regressing biological age measurement, which was constructed based on baseline 16 physical and 9 biochemical markers using Klemera and Doubal's method, on chronological age. We estimated the associations of KDM-AA with the mortality risk using the hazard ratio (HR) and 95% confidence interval (CI) from Cox proportional hazard models. We assessed discrimination performance by Harrell's C-index and net reclassification index (NRI).
Findings The participants who developed MCE (mean KDM-AA = 0.1 year, standard deviation [SD] = 1.6 years) or ICH/SAH (0.3 ± 1.5 years) during subsequent follow-up showed accelerated aging at baseline compared to those of IS (0.0 ± 1.2 years) and control (−0.3 ± 1.3 years) groups. The KDM-AA was positively associated with long-term risk of all-cause mortality (HR = 1.20; 95% CI: 1.17, 1.23), and the association was robust for participants potentially at different stages of the CVD continuum. Adding KDM-AA improved mortality prediction compared to the model only with sociodemographic and lifestyle factors in whole participants, with the Harrell's C-index increasing from 0.813 (0.807, 0.819) to 0.821 (0.815, 0.826) (NRI = 0.011; 95% CI: 0.003, 0.019).
Interpretation In this middle-aged and elderly Chinese population, the KDM-AA is a promising measurement for biological age, and can capture the difference in cardiovascular health and predict the risk of all-cause mortality over a decade.
Funding This work was supported by National Natural Science Foundation of China (82192904, 82192901, 82192900, 81941018). The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303), and Chinese Ministry of Science and Technology (2011BAI09B01)
High-efficiency and broadband electro-optic frequency combs enabled by coupled micro-resonators
Developments in integrated photonics have led to stable, compact, and
broadband comb generators that support a wide range of applications. Current
on-chip comb generators, however, are still limited by low optical pump-to-comb
conversion efficiencies. Here, we demonstrate an integrated electro-optic
frequency comb with a conversion efficiency of 30% and an optical bandwidth of
132 nm, featuring a 100-times higher conversion efficiency and 2.2-times
broader optical bandwidth compared with previous state-of-the-art integrated
electro-optic combs. We further show that, enabled by the high efficiency, the
device acts as an on-chip femtosecond pulse source (336 fs pulse duration),
which is important for applications in nonlinear optics, sensing, and
computing. As an example, in the ultra-fast and high-power regime, we
demonstrate the observation of a combined EO-\chi^(3) nonlinear frequency comb.
Our device paves the way for practical optical frequency comb generators
enabling energy-efficient computing, communication, and metrology, and provides
a platform to investigate new regimes of optical physics that simultaneously
involve multiple nonlinearities
Integrated Electro-Optic Isolator on Thin Film Lithium Niobate
Optical isolator is an indispensable component of almost any optical system
and is used to protect a laser from unwanted reflections for phase-stable
coherent operation. The development of chip-scale optical systems, powered by
semiconductor lasers integrated on the same chip, has resulted in a need for a
fully integrated optical isolator. However, conventional approaches based on
application of magneto-optic materials to break the reciprocity and provide
required isolation have significant challenges in terms of material processing
and insertion loss. As a result, many magnetic-free approaches have been
explored, including acousto-optics, optical nonlinearity, and electro-optics.
However, to date, the realization of an integrated isolator with low insertion
loss, high isolation ratio, broad bandwidth, and low power consumption on a
monolithic material platform is still absent. Here we realize non-reciprocal
traveling-wave EO-based isolator on thin-film LN, enabling maximum optical
isolation of 48 dB and an on-chip insertion loss of 0.5 dB using a
single-frequency microwave drive at 21-dBm RF power. The isolation ratio is
verified to be larger than 37 dB across a tunable optical wavelength range from
1510 to 1630 nm. We verify that our hybrid DFB laser - LN isolator module
successfully protects the single-mode operation and the linewidth of the DFB
laser from reflection. Our result is a significant step towards a practical
high-performance optical isolator on chip
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