Search results for: molecular imaging

Authors: Sankarprasad Bhuniya, Sukhendu Maiti, Eun-Joong Kim, Hyunseung Lee, Jonathan L. Sessler, Kwan Soo Hong, Jong Seung Kim

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A new theranostic strategy is described. It is based on the use of an “all in one” prodrug, namely the biotinylated piperazine-rhodol conjugate 4a. This conjugate, which incorporates the anticancer drug SN-38, undergoes self-immolative cleavage when exposed to biological thiols. This leads to the tumor-targeted release of the active SN-38 payload along with fluorophore 1a. This release is made selective as the result of the biotin functionality. Fluorophore 1a is 32-fold more fluorescent than prodrug 4a. It permits the delivery and release of the SN-38 payload to be monitored easily in vitro and in vivo, as inferred from cell studies and ex vivo analyses of mice xenografts derived HeLa cells, respectively. Prodrug 4a also displays anticancer activity in the HeLa cell murine xenograft tumor model. On the basis of these findings we suggest that the present strategy, which combines within a single agent the key functions of targeting, release, imaging, and treatment, may have a role to play in cancer diagnosis and therapy.

Keywords: theranostic, prodrug, cancer therapy, fluorescence

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Authors: Paramita Banerjee, K. R. S. Chandrakumar, G. P. Das

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Bulk MgH2 has drawn much attention for the purpose of hydrogen storage because of its high hydrogen storage capacity (~7.7 wt %) as well as low cost and abundant availability. However, its practical usage has been hindered because of its high hydrogen desorption enthalpy (~0.8 eV/H2 molecule), which results in an undesirable desorption temperature of 3000C at 1 bar H2 pressure. To surmount the limitations of bulk MgH2 for the purpose of hydrogen storage, a detailed first-principles density functional theory (DFT) based study on the structure and stability of neutral (Mgm) and positively charged (Mgm+) Mg nanoclusters of different sizes (m = 2, 4, 8 and 12), as well as their interaction with molecular hydrogen (H2), is reported here. It has been found that due to the absence of d-electrons within the Mg atoms, hydrogen remained in molecular form even after its interaction with neutral and charged Mg nanoclusters. Interestingly, the H2 molecules do not enter into the interstitial positions of the nanoclusters. Rather, they remain on the surface by ornamenting these nanoclusters and forming new structures with a gravimetric density higher than 15 wt %. Our observation is that the inclusion of Grimme’s DFT-D3 dispersion correction in this weakly interacting system has a significant effect on binding of the H2 molecules with these nanoclusters. The dispersion corrected interaction energy (IE) values (0.1-0.14 eV/H2 molecule) fall in the right energy window, that is ideal for hydrogen storage. These IE values are further verified by using high-level coupled-cluster calculations with non-iterative triples corrections i.e. CCSD(T), (which has been considered to be a highly accurate quantum chemical method) and thereby confirming the accuracy of our ‘dispersion correction’ incorporated DFT calculations. The significance of the polarization and dispersion energy in binding of the H2 molecules are confirmed by performing energy decomposition analysis (EDA). A total of 16, 24, 32 and 36 H2 molecules can be attached to the neutral and charged nanoclusters of size m = 2, 4, 8 and 12 respectively. Ab-initio molecular dynamics (AIMD) simulation shows that the outermost H2 molecules are desorbed at a rather low temperature viz. 150 K (-1230C) which is expected. However, complete dehydrogenation of these nanoclusters occur at around 1000C. Most importantly, the host nanoclusters remain stable up to ~500 K (2270C). All these results on the adsorption and desorption of molecular hydrogen with neutral and charged Mg nanocluster systems indicate towards the possibility of reducing the dehydrogenation temperature of bulk MgH2 by designing new Mg-based nano materials which will be able to adsorb molecular hydrogen via this weak Mg-H2 interaction, rather than the strong Mg-H bonding. Notwithstanding the fact that in practical applications, these interactions will be further complicated by the effect of substrates as well as interactions with other clusters, the present study has implications on our fundamental understanding to this problem.

Keywords: density functional theory, DFT, hydrogen storage, molecular dynamics, molecular hydrogen adsorption, nanoclusters, physisorption

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Authors: K. Ali, M. F. Qamar, M. A. Zaman, M. Younus, I. Khan, S. Ehtisham-ul-Haque, R. Tamkeen, M. I. Rashid, Q. Ali

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This study centers on molecular identification of Haemonchus contortus and isolation of Benz-imidazoles (BZ) resistant strains. Different abattoirs’ of two geographic regions of Punjab (Pakistan) were frequently visited for the collection of worms. Out of 1500 (n=1500) samples that were morphologically confirmed as H. contortus, 30 worms were subjected to molecular procedures for isolation of resistant strains. Resistant worms (n=8) were further subjected to DNA gene sequencing. Bio edit sequence alignment editor software was used to detect the possible mutation, deletion, replacement of nucleotides. Genetic diversity was noticed and genetic variation existing in β-tubulin isotype 1 of the H. contortus population of small ruminants of different regions considered in this study. H. contortus showed three different type of genetic sequences. 75%, 37.5%, 25% and 12.5% of the studied samples showed 100% query cover and identity with isolates and clones of China, UK, Australia and other countries, respectively. Interestingly the neighbor countries such as India and Iran haven’t many similarities with the Pakistani isolates. Thus, it suggests that population density of same genetic makeup H. contortus is scattered worldwide rather than clustering in a single region.

Keywords: Haemonchus contortus, Benzimidazole resistant, β-tubulin-1 gene, abattoirs

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Authors: Chhabi Nigam, S. Ramakrishnan

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This paper brings out the analysis of the airborne Synthetic Aperture Radar (SAR) data to study the impact of Doppler centroid on Image quality and geocoding accuracy from the perspective of Stripmap mode of data acquisition. Although in Stripmap mode of data acquisition radar beam points at 90 degrees broad side (side looking), shift in the Doppler centroid is invariable due to platform motion. In-accurate estimation of Doppler centroid leads to poor image quality and image miss-registration. The effect of Doppler centroid is analyzed in this paper using multiple sets of data collected from airborne platform. Occurrences of ghost (ambiguous) targets and their power levels have been analyzed that impacts appropriate choice of PRF. Effect of aircraft attitudes (roll, pitch and yaw) on the Doppler centroid is also analyzed with the collected data sets. Various stages of the RDA (Range Doppler Algorithm) algorithm used for image formation in Stripmap mode, range compression, Doppler centroid estimation, azimuth compression, range cell migration correction are analyzed to find the performance limits and the dependence of the imaging geometry on the final image. The ability of Doppler centroid estimation to enhance the imaging accuracy for registration are also illustrated in this paper. The paper also tries to bring out the processing of low squint SAR data, the challenges and the performance limits imposed by the imaging geometry and the platform dynamics on the final image quality metrics. Finally, the effect on various terrain types, including land, water and bright scatters is also presented.

Keywords: ambiguous target, Doppler Centroid, image registration, Airborne SAR

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Authors: Ethan James

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Over one billion people worldwide suffer from some level of vision loss or blindness as a result of progressive retinal diseases. Many patients, particularly in developing areas, are incorrectly diagnosed or undiagnosed whatsoever due to unconventional diagnostic tools and screening methods. Artificial intelligence (AI) based on deep learning (DL) convolutional neural networks (CNN) have recently gained a high interest in ophthalmology for its computer-imaging diagnosis, disease prognosis, and risk assessment. Optical coherence tomography (OCT) is a popular imaging technique used to capture high-resolution cross-sections of retinas. In ophthalmology, DL has been applied to fundus photographs, optical coherence tomography, and visual fields, achieving robust classification performance in the detection of various retinal diseases including macular degeneration, diabetic retinopathy, and retinitis pigmentosa. However, there is no complete diagnostic model to analyze these retinal images that provide a diagnostic accuracy above 90%. Thus, the purpose of this project was to develop an AI model that utilizes machine learning techniques to automatically diagnose specific retinal diseases from OCT scans. The algorithm consists of neural network architecture that was trained from a dataset of over 20,000 real-world OCT images to train the robust model to utilize residual neural networks with cyclic pooling. This DL model can ultimately aid ophthalmologists in diagnosing patients with these retinal diseases more quickly and more accurately, therefore facilitating earlier treatment, which results in improved post-treatment outcomes.

Keywords: artificial intelligence, deep learning, imaging, medical devices, ophthalmic devices, ophthalmology, retina

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Authors: Sergio Alejandro Cuevas, Catherine Etchebest, Fernando Luis Barroso Da Silva

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The flavivirus genus has several organisms responsible for generating various diseases in humans. Special in Brazil, Zika (ZIKV), Dengue (DENV) and Yellow Fever (YFV) viruses have raised great health concerns due to the high number of cases affecting the area during the last years. Diagnostic is still a difficult issue since the clinical symptoms are highly similar. The understanding of their common structural/dynamical and biomolecular interactions features and differences might suggest alternative strategies towards differential serological diagnostics and therapeutic intervention. Due to their immunogenicity, the primary focus of this study was on the ZIKV, DENV and YFV non-structural proteins 1 (NS1) protein. By means of computational studies, we calculated the main physical chemical properties of this protein from different strains that are directly responsible for the biomolecular interactions and, therefore, can be related to the differential infectivity of the strains. We also mapped the electrostatic differences at both the sequence and structural levels for the strains from Uganda to Brazil that could suggest possible molecular mechanisms for the increase of the virulence of ZIKV. It is interesting to note that despite the small changes in the protein sequence due to the high sequence identity among the studied strains, the electrostatic properties are strongly impacted by the pH which also impact on their biomolecular interactions with partners and, consequently, the molecular viral biology. African and Asian strains are distinguishable. Exploring the interfaces used by NS1 to self-associate in different oligomeric states, and to interact with membranes and the antibody, we could map the strategy used by the ZIKV during its evolutionary process. This indicates possible molecular mechanisms that can explain the different immunological response. By the comparison with the known antibody structure available for the West Nile virus, we demonstrated that the antibody would have difficulties to neutralize the NS1 from the Brazilian strain. The present study also opens up perspectives to computationally design high specificity antibodies.

Keywords: zika, biomolecular interactions, electrostatic interactions, molecular mechanisms

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Authors: Radoslav Stojchevski, Leonid Poretsky, Dimiter Avtanski

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Proinflammatory cytokines play an important role in cancer initiation and progression by mediating the intracellular communication between the cancer cells and tumor microenvironment. Increased tumor growth causing reduced oxygen concentration and oxygen pressure commonly result in hypoxia. Mechanistically, hypoxia is characterized by stabilization and nuclear translocation of hypoxia-inducible factor 1 alpha (HIF-1α) followed by propagation of molecular pathway cascade involving multiple downstream targets. Cobalt(II) chloride (CoCl₂) is commonly used to mimic hypoxia in experimental conditions since it directly induces the expression of HIF-1α. The aim of the present study was to investigate the in vitro effects and the molecular mechanisms by which hypoxia regulates the cytokine secretory profile of breast cancer cells. As a model for this study, we used several breast cancer cell lines bearing various molecular characteristics and metastatic potential (MDA-MB-231 (clauding low, ER-/PR-/HER²⁻), MCF-7 (luminal A, ER⁺/PR⁺/HER²⁻), and BT-474 (liminal B, ER⁺/PR⁺/HER²⁺)). We demonstrated that breast cancer cells secrete numerous cytokines and cytokine ligands, including interleukins, chemokines, and growth factors. Treatment with CoCl₂significantly modulated the breast cancer cells' cytokine expression in a concentration- and time-dependent manner. These effects were mediated via activation of several signaling pathways (JNK/SAPK1, NF-κB, STAT5A/B, and Erk/MAPK1/2). Taken together, the present data define some of the molecular mechanisms by which hypoxia affects the breast cancer cells' cytokine secretory profile, thus contributing to the development of novel therapies for metastatic breast cancer.

Keywords: breast cancer, cytokines, cobalt(II) chloride (CoCl₂), hypoxia

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Authors: Brayden Mi

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Reverse time migration has been widely used in the Petroleum exploration industry to reveal subsurface images and to detect rock and fluid properties since the early 1980s. The seismic technology involves the construction of a velocity model through interpretive model construction, seismic tomography, or full waveform inversion, and the application of the reverse-time propagation of acquired seismic data and the original wavelet used in the acquisition. The methodology has matured from 2D, simple media to present-day to handle full 3D imaging challenges in extremely complex geological conditions. Conventional Ultrasound computed tomography (USCT) utilize travel-time-inversion to reconstruct the velocity structure of an organ. With the velocity structure, USCT data can be migrated with the “bend-ray” method, also known as migration. Its seismic application counterpart is called Kirchhoff depth migration, in which the source of reflective energy is traced by ray-tracing and summed to produce a subsurface image. It is well known that ray-tracing-based migration has severe limitations in strongly heterogeneous media and irregular acquisition geometries. Reverse time migration (RTM), on the other hand, fully accounts for the wave phenomena, including multiple arrives and turning rays due to complex velocity structure. It has the capability to fully reconstruct the image detectable in its acquisition aperture. The RTM algorithms typically require a rather accurate velocity model and demand high computing powers, and may not be applicable to real-time imaging as normally required in day-to-day medical operations. However, with the improvement of computing technology, such a computational bottleneck may not present a challenge in the near future. The present-day (RTM) algorithms are typically implemented from a flat datum for the seismic industry. It can be modified to accommodate any acquisition geometry and aperture, as long as sufficient illumination is provided. Such flexibility of RTM can be conveniently implemented for the application in USCT imaging if the spatial coordinates of the transmitters and receivers are known and enough data is collected to provide full illumination. This paper proposes an implementation of a full 3D RTM algorithm for USCT imaging to produce an accurate 3D acoustic image based on the Phase-shift-plus-interpolation (PSPI) method for wavefield extrapolation. In this method, each acquired data set (shot) is propagated back in time, and a known ultrasound wavelet is propagated forward in time, with PSPI wavefield extrapolation and a piece-wise constant velocity model of the organ (breast). The imaging condition is then applied to produce a partial image. Although each image is subject to the limitation of its own illumination aperture, the stack of multiple partial images will produce a full image of the organ, with a much-reduced noise level if compared with individual partial images.

Keywords: illumination, reverse time migration (RTM), ultrasound computed tomography (USCT), wavefield extrapolation

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Authors: Azza T. Tahera, Eman M. Ahmeda, Nadia A. Khalila, Yassin M. Nissanb

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New 3-(pyridin-4-yl)-[1,2,4] triazolo [4,3-b] pyridazine derivatives 2a-i, 4a,b and 6a,b were designed, synthesized and evaluated as cytotoxic agents. All compounds were investigated for their in vitro cytotoxicity at a single dose 10-5M concentration towards 60 cancer cell lines according to USA NCI protocol. The preliminary screening results showed that the majority of tested compounds exhibited remarkable activity against SR (leukemia) cell panel. Molecular docking for all synthesized compounds was performed on the active site of c-Met kinase. The most active compounds, 2f and 4a were further evaluated at a seven dose level screening and their IC50 as a c-Met kinase inhibitors were determined in vitro.

Keywords: triazolopyridazines, pyridazines, cytotoxic activity, cell panel

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Authors: Pyar S. Jassal, Sonal Gupta, Neema Chand, Rajni Johar

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In present study, Low molecular weight chitosan naoparticles (LMWCNP) were synthesized by using low molecular weight chitosan (LMWC) and sodium tripolyphosphate for the adsorption of anthraquinone dyes from waste water. The ionic-gel technique was used for this purpose. Size of nanoparticles was determined by “Scherrer equation”. The absorbance was carried out with UV-visible spectrophotometer for Acid Green 25 (AG25) and Reactive Blue 4 (RB4) dyes solutions at λmax 644 and λmax 598 nm respectively. The removal of dyes was dependent on the pH and the optimum adsorption was between pH 2 to 9. The extraction of dyes was linearly dependent on temperature. The equilibrium parameters, RL was calculated by using the Langmuir isotherm and shows that adsorption of dyes is favorable on the LMWCNP. The XRD images of LMWC show a crystalline nature whereas LMWCNP is amorphous one. The thermo gravimetric analysis (TGA) shows that LMWCNP thermally more stable than LMWC. As the contact time increases, percentage removal of Acid Green 25 and Reactive Blue 4 dyes also increases. TEM images reveal the size of the LMWCNP were in the range of 45-50 nm. The capacity of AG25 dye on LMWC was 5.23 mg/g, it compared with LMWCNP capacity which was 6.83 mg/g respectively. The capacity of RB4 dye on LMWC was 2.30 mg/g and 2.34 mg/g was on LMWCNP.

Keywords: low molecular weight chitosan nanoparticles, anthraquinone dye, removal efficiency, adsorption isotherm

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Authors: Madeleine Anthonisen, M. Hussain Sangji, G. Monserratt Lopez-Ayon, Margaret Magdesian, Peter Grutter

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Advances in micromanipulation techniques and real-time particle tracking with nanometer resolution have enabled biological force measurements at scales relevant to neuron mechanics. An approach to precisely control and maneuver neurite-tethered polystyrene beads is presented. Analogous to an Atomic Force Microscope (AFM), this multi-purpose platform is a force sensor with imaging acquisition and manipulation capabilities. A mechanical probe composed of a micropipette with its tip fixed to a functionalized bead is used to incite the formation of a neurite in a sample of rat hippocampal neurons while simultaneously measuring the tension in said neurite as the sample is pulled away from the beaded tip. With optical imaging methods, a force resolution of 12 pN is achieved. Moreover, the advantages of this technique over alternatives such as AFM, namely ease of manipulation which ultimately allows higher throughput investigation of the mechanical properties of neurons, is demonstrated.

Keywords: axonal growth, axonal guidance, force probe, pipette micromanipulation, neurite tension, neuron mechanics

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Authors: Anita Yaghobi, Homayoun Ebrahimian

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One of the important tools that can help orthopedic doctors for diagnose diseases is imaging scan. Imaging techniques can help physicians in see different parts of the body, including the bones, muscles, tendons, nerves, and cartilage. During CT scan, a patient must be in the same position from the start to the end of radiation treatment. Patient movements are usually monitored by the technologists through the closed circuit television (CCTV) during scan. If the patient makes a small movement, it is difficult to be noticed by them. In the present work, a simple patient movement monitoring device is fabricated to monitor the patient movement. It uses an electronic sensing device. It continuously monitors the patient’s position while the CT scan is in process. The device has been retrospectively tested on 51 patients whose movement and distance were measured. The results show that 25 patients moved 1 cm to 2.5 cm from their initial position during the CT scan. Hence, the device can potentially be used to control and monitor patient movement during CT scan and Radiography. In addition, an audible alarm situated at the control panel of the control room is provided with this device to alert the technologists. It is an inexpensive, compact device which can be used in any CT scan machine.

Keywords: CT scan, radiology, X Ray, unwanted movement

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Authors: Sudhir Kumar Sharma, Ramesh Jagannathan

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The interaction of organic and inorganic matrices of biological origin resulting in self-assembled structures with unique properties is well established. The development of such self-assembled nanostructures by synthetic and bio-inspired techniques is an established field of active research. Among bio-materials, nacre, a laminar stack of calcium carbonate nanosheets, which are interleaved with organic material, has long been focused research due to its unique mechanical properties. In this paper, we present the development of nacre-like lamellar structures made up of calcium carbonate via a wet chemical route. We used the binding affinity of carboxylate anions and calcium cations using poly (acrylic) acid (PAA) to lead CaCO₃ crystallization. In these experiments, we selected calcium acetate as the precursor molecule along with PAA (Mw ~ 8000 Da). We found that Ca⁺²/COO⁻ ratio provided a tunable control for the morphology and growth of CaCO₃ nanostructures. Drop casting one such formulation on a silicon substrate followed by calcination resulted in co-planner, molecular sheets of CaCO₃, separated by a spacer layer of carbon. The scope of our process could be expanded to produce unit cell thick molecular sheets of other important inorganic materials.

Keywords: self-assembled structures, bio-inspired materials, calcium carbonate, wet chemical route

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Authors: Alireza Jalalvand, Maryam Saleh, Somayeh Behjat Khatouni, Zahra Bahri Najafi, Foroozan Fatahinia, Narges Ismailzadeh, Behrokh Farahmand

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Object: In the last two decades, the recent outbreak of Coronavirus (SARS-CoV-2) imposed a global pandemic in the world. Despite the increasing prevalence of the disease, there are no effective drugs to treat it. A suitable and rapid way to afford an effective drug and treat the global pandemic is a computational drug study. This study used molecular docking methods to examine the potential inhibition of over 50 antiviral drugs against three fundamental proteins of SARS-CoV-2. METHODS: Through a literature review, three important proteins (a key protease, RNA-dependent RNA polymerase (RdRp), and spike) were selected as drug targets. Three-dimensional (3D) structures of protease, spike, and RdRP proteins were obtained from the Protein Data Bank. Protein had minimal energy. Over 50 antiviral drugs were considered candidates for protein inhibition and their 3D structures were obtained from drug banks. The Autodock 4.2 software was used to define the molecular docking settings and run the algorithm. RESULTS: Five drugs, including indinavir, lopinavir, saquinavir, nelfinavir, and remdesivir, exhibited the highest inhibitory potency against all three proteins based on the binding energies and drug binding positions deduced from docking and hydrogen-bonding analysis. Conclusions: According to the results, among the drugs mentioned, saquinavir and lopinavir showed the highest inhibitory potency against all three proteins compared to other drugs. It may enter laboratory phase studies as a dual-drug treatment to inhibit SARS-CoV-2.

Keywords: covid-19, drug repositioning, molecular docking, lopinavir, saquinavir

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Authors: Matheus Madureira Matos, Alexandre Rodrigues Farias

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Magnetic Resonance Imaging (MRI) is a vital imaging technique used in both clinical and pre-clinical areas to obtain detailed anatomical and functional information. However, MRI scans can be expensive, time-consuming, and often require the use of anesthetics to keep animals still during the imaging process. Anesthetics are commonly administered to animals undergoing MRI scans to ensure they remain still during the imaging process. However, prolonged or repeated exposure to anesthetics can have adverse effects on animals, including physiological alterations and potential toxicity. Minimizing the duration and frequency of anesthesia is, therefore, crucial for the well-being of research animals. In recent years, various sampling trajectories have been investigated to reduce the number of MRI measurements leading to shorter scanning time and minimizing the duration of animal exposure to the effects of anesthetics. Compressed sensing (CS) and sampling trajectories, such as cartesian, spiral, and radial, have emerged as powerful tools to reduce MRI data while preserving diagnostic quality. This work aims to apply CS and cartesian, spiral, and radial sampling trajectories for the reconstruction of MRI of the abdomen of mice sub-sampled at levels below that defined by the Nyquist theorem. The methodology of this work consists of using a fully sampled reference MRI of a female model C57B1/6 mouse acquired experimentally in a 4.7 Tesla MRI scanner for small animals using Spin Echo pulse sequences. The image is down-sampled by cartesian, radial, and spiral sampling paths and then reconstructed by CS. The quality of the reconstructed images is objectively assessed by three quality assessment techniques RMSE (Root mean square error), PSNR (Peak to Signal Noise Ratio), and SSIM (Structural similarity index measure). The utilization of optimized sampling trajectories and CS technique has demonstrated the potential for a significant reduction of up to 70% of image data acquisition. This result translates into shorter scan times, minimizing the duration and frequency of anesthesia administration and reducing the potential risks associated with it.

Keywords: compressed sensing, magnetic resonance, sampling trajectories, small animals

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Authors: Chro Kawyan

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Endothelin-1 (ET-1), the principal individual from the newfound mammalian endothelin group of organically dynamic peptides, was initially distinguished as a 21 buildup powerful vasoconstrictor peptide in vascular endothelial cells. However, it has since been demonstrated to have a wide range of pharmacological activities in tissues both inside and outside the cardiovascular system. Additionally, peptides that have a striking resemblance to ET-1 have been identified as the primary toxic component of snake venom. In addition, late examinations have proposed that warm blooded creatures, including people, produce three unmistakable individuals from this peptide family, ET-1, ET-2 and ET-J, which might have various profiles of organic action and may follow up on particular subtypes of endothelin receptor. Masashi Yanagisawa and Tomoh Masaki survey the ongoing status of the organic chemistry and sub-atomic science of endothelin.

Keywords: thelin, microbiology, molecular biology, cell

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Authors: G. V. Novikov, V. S. Sivozhelezov, S. S. Kolesnikov, K. V. Shaitan

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The study reports about the influence of binding of orthosteric ligands as well as point mutations on the conformational dynamics of β-2-adrenoreceptor. Using molecular dynamics simulation we found that there was a little fraction of active states of the receptor in its apo (ligand free) ensemble corresponded to its constitutive activity. Analysis of MD trajectories indicated that such spontaneous activation of the receptor is accompanied by the motion in intracellular part of its alpha-helices. Thus receptor’s constitutive activity directly results from its conformational dynamics. On the other hand the binding of a full agonist resulted in a significant shift of the initial equilibrium towards its active state. Finally, the binding of the inverse agonist stabilized the receptor in its inactive state. It is likely that the binding of inverse agonists might be a universal way of constitutive activity inhibition in vivo. Our results indicate that ligand binding redistribute pre-existing conformational degrees of freedom (in accordance to the Monod-Wyman-Changeux-Model) of the receptor rather than cause induced fit in it. Therefore, the ensemble of biologically relevant receptor conformations is encoded in its spatial structure, and individual conformations from that ensemble might be used by the cell in conformity with the physiological behaviour.

Keywords: seven-transmembrane receptors, constitutive activity, activation, x-ray crystallography, principal component analysis, molecular dynamics simulation

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Authors: Matej Patzelt, Jan Dudak, Frantisek Krejci, Jan Zemlicka, Vladimir Musil, Jitka Riedlova, Viktor Sykora, Jana Mrzilkova, Petr Zach

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Introduction: Micro-CT is well used for examination of bone structures and teeth. On the other hand visualization of the soft tissues is still limited. The goal of our study was to create a new fixation method for soft tissue imaging in micro-CT. Methodology: We used organs of 18 mice - heart, lungs, kidneys, liver and brain, which we fixated in ethanol after meticulous preparation. We fixated organs in different concentrations of ethanol and for different period of time. We used three types of ethanol concentration - 97%, 50% and ascending ethanol concentration (25%, 50%, 75%, 97% each for 12 hours). Fixated organs were scanned after 72 hours, 168 hours and 336 hours period of fixation. We scanned all specimens in micro-CT MARS (Medipix All Resolution System). Results: Ethanol method provided contrast enhancement in all studied organs in all used types of fixation. Fixation in 97% ethanol provided very fast fixation and the contrast among the tissues was visible already after 72 hours of fixation. Fixation for the period of 168 and 336 hours gave better details, especially in lung tissue, where alveoli were visualized. On the other hand, this type of fixation caused organs to petrify. Fixation in 50% ethanol provided best results in 336 hours fixation, details were visualized better than in 97% ethanol and samples were not as hard as in fixation in 97% ethanol. Best results were obtained in fixation in ascending ethanol concentration. All organs were visualized in great details, best-visualized organ was heart, where trabeculae and valves were visible. In this type of fixation, organs stayed soft for whole time. Conclusion: New ethanol method is a great option for soft tissue fixation as well as the method for enhancing contrast among tissues in organs. The best results were obtained with fixation of the organs in ascending ethanol concentration, the best visualized organ was the heart.

Keywords: x-ray imaging, small animals, ethanol, ex-vivo

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Authors: Babak Safaei, A. M. Fattahi

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In the present study we have investigated axial buckling characteristics of nanocomposite beams reinforced by single-walled carbon nanotubes (SWCNTs). Various types of beam theories including Euler-Bernoulli beam theory, Timoshenko beam theory and Reddy beam theory were used to analyze the buckling behavior of carbon nanotube-reinforced composite beams. Generalized differential quadrature (GDQ) method was utilized to discretize the governing differential equations along with four commonly used boundary conditions. The material properties of the nanocomposite beams were obtained using molecular dynamic (MD) simulation corresponding to both short-(10,10) SWCNT and long-(10,10) SWCNT composites which were embedded by amorphous polyethylene matrix. Then the results obtained directly from MD simulations were matched with those calculated by the mixture rule to extract appropriate values of carbon nanotube efficiency parameters accounting for the scale-dependent material properties. The selected numerical results were presented to indicate the influences of nanotube volume fractions and end supports on the critical axial buckling loads of nanocomposite beams relevant to long- and short-nanotube composites.

Keywords: nanocomposites, molecular dynamics simulation, axial buckling, generalized differential quadrature (GDQ)

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Authors: Niloufar Yadgari

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GANs are a potent form of deep learning models that have found success in various fields. They are part of the larger group of generative techniques, which aim to produce authentic data using a probabilistic model that learns distributions from actual samples. In clinical settings, GANs have demonstrated improved abilities in capturing spatially intricate, nonlinear, and possibly subtle disease impacts in contrast to conventional generative techniques. This review critically evaluates the current research on how GANs are being used in imaging studies of different neurological conditions like Alzheimer's disease, brain tumors, aging of the brain, and multiple sclerosis. We offer a clear explanation of different GAN techniques for each use case in neuroimaging and delve into the key hurdles, unanswered queries, and potential advancements in utilizing GANs in this field. Our goal is to connect advanced deep learning techniques with neurology studies, showcasing how GANs can assist in clinical decision-making and enhance our comprehension of the structural and functional aspects of brain disorders.

Keywords: GAN, pathology, generative adversarial network, neuro imaging

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Authors: Paromik Bhattacharyya, Vijay Kumar, Johannes Van Staden

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Micropropagation is an important tool for the conservation of threatened and commercially important plant species of which orchids deserve special attention. Ansellia africana is one such medicinally important orchid species having much commercial significance. Thus, development of regeneration protocols for producing clonally stable regenerates using axillary buds is of much importance. However, for large-scale micropropagation to become not only successful but also acceptable by end-users, somaclonal variations occurring in the plantlets need to be eliminated. In the light of the various factors (genotype, ploidy level, in vitro culture age, explant and culture type, etc.) that may account for the somaclonal variations of divergent genetic changes at the cellular and molecular levels, genetic analysis of micropropagated plants using a multidisciplinary approach is of utmost importance. In the present study, the clonal integrity of the long term micropropagated A. africana plants were assessed using advanced molecular marker system i.e. Start Codon Targeted Polymorphism (SCoT). Our studies recorded a clonally stable regeneration protocol for A. africana with a very high degree of clonal fidelity amongst the regenerates. The results obtained from these molecular analyses could help in modifying the regeneration protocols for obtaining clonally stable true to type plantlets for sustainable commercial use.

Keywords: medicinal orchid micropropagation, start codon targeted polymorphism (SCoT), RAP), traditional African pharmacopoeia, genetic fidelity

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Authors: Mariam Mojally, Randa Abdou, Wisal Bokhari, Sultan Sab, Mohammed Dawoud, Amjad Albohy

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Secondary metabolites produced by endophytes are an excellent source of biologically active compounds. In our current study, we evaluated terezine E and 14-hydroxyterezine D for binding to the active site of histone deacetylase (PDB ID: 4CBT) and matrix metalloproteinase 9 (PDB ID: 4H3X) by molecular docking using AutoDock Vina software after having tested their cytotoxic activities on three cell lines (human ductal breast epithelial tumor cells (T47D)-HCC1937), human hepatocarcinoma cell line (HepG2)-HB8065), and human colorectal carcinoma cells (HCT-116)-TCP1006, purchased from ATCC, USA)). Additionally, their antimicrobial activities were investigated, and their minimum inhibitory concentration (MIC) values were determined against P. notatum and S. aureus by the broth microdilution method. Higher cytotoxicity was observed for terezine E against all tested cell lines compared to 14-hydroxyterezine D. Molecular docking results supported the high cytotoxicity of terezine E and showed higher binding affinity with 4CBT with an energy score of 9 kcal/mol. Terezine E showed higher antibacterial and antifungal activities than 14-hydroxyrerezine D: MIC values were 15.45 and 21.73 mg/mL against S. aureus and 8.61 and 11.54 mg/mL against P. notatum, respectively

Keywords: Terezine E, 14-Hydroxyterezine D, cytotoxicity, antimicrobial activity, molecular docking

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Authors: Sukriti Sabharwal, Sonali Bhattar, Shikhar Saxena

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Introduction: COVID-19 molecular diagnostic laboratory is the cornerstone of the COVID-19 disease diagnosis as the patient’s treatment and management protocol depend on the molecular results. For this purpose, it is extremely important that the laboratory conducting these results adheres to the quality management processes to increase the accuracy and validity of the reports generated. We started our own molecular diagnostic setup at the onset of the pandemic. Therefore, we conducted this study to generate our quality management data to help us in improving on our weak points. Materials and Methods: A total of 14561 samples were evaluated by the retrospective observational method. The quality variables analysed were classified into pre-analytical, analytical, and post-analytical variables, and the results were presented in percentages. Results: Among the pre-analytical variables, sample leaking was the most common cause of the rejection of samples (134/14561, 0.92%), followed by non-generation of SRF ID (76/14561, 0.52%) and non-compliance to triple packaging (44/14561, 0.3%). The other pre-analytical aspects assessed were incomplete patient identification (17/14561, 0.11%), insufficient quantity of samples (12/14561, 0.08%), missing forms/samples (7/14561, 0.04%), samples in the wrong vials/empty VTM tubes (5/14561, 0.03%) and LIMS entry not done (2/14561, 0.01%). We are unable to obtain internal quality control in 0.37% of samples (55/14561). We also experienced two incidences of cross-contamination among the samples resulting in false-positive results. Among the post-analytical factors, a total of 0.07% of samples (11/14561) could not be dispatched within the stipulated time frame. Conclusion: Adherence to quality control processes is foremost for the smooth running of any diagnostic laboratory, especially the ones involved in critical reporting. Not only do the indicators help in keeping in check the laboratory parameters but they also allow comparison with other laboratories.

Keywords: laboratory quality management, COVID-19, molecular diagnostics, healthcare

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Authors: Alisha M. Ebrahim, Bijoy K. Menon, Eddy Lang, Shelagh B. Coutts, Katie Lin

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Introduction: Frontline emergency physicians require clear and evidence-based approaches to guide neuroimaging investigations for patients presenting with suspected acute stroke or transient ischemic attack (TIA). Various forms of computed tomography (CT) are currently available for initial investigation, including non-contrast CT (NCCT), CT angiography head and neck (CTA), and CT perfusion (CTP). However, there is uncertainty around optimal imaging choice for cost-effectiveness, particularly for minor or resolved neurological symptoms. In addition to the cost of CTA and CTP testing, there is also a concern for increased incidental findings, which may contribute to the burden of overdiagnosis. Methods: In this cross-sectional observational study, analysis was conducted on 586 anonymized triage and diagnostic imaging (DI) reports for neuroimaging orders completed on patients presenting to adult emergency departments (EDs) with a suspected stroke or TIA from January-December 2019. The primary outcome of interest is the diagnostic yield of NCCT+CTA compared to NCCT alone for patients presenting to urban academic EDs with Canadian Emergency Department Information System (CEDIS) complaints of “symptoms of stroke” (specifically acute stroke and TIA indications). DI reports were coded into 4 pre-specified categories (endorsed by a panel of stroke experts): no abnormalities, clinically significant findings (requiring immediate or follow-up clinical action), incidental findings (not meeting prespecified criteria for clinical significance), and both significant and incidental findings. Standard descriptive statistics were performed. A two-sided p-value <0.05 was considered significant. Results: 75% of patients received NCCT+CTA imaging, 21% received NCCT alone, and 4% received NCCT+CTA+CTP. The diagnostic yield of NCCT+CTA imaging for prespecified clinically significant findings was 24%, compared to only 9% in those who received NCCT alone. The proportion of incidental findings was 30% in the NCCT only group and 32% in the NCCT+CTA group. CTP did not significantly increase the yield of significant or incidental findings. Conclusion: In this cohort of patients presenting with suspected stroke or TIA, an NCCT+CTA neuroimaging strategy had a higher diagnostic yield for clinically significant findings than NCCT alone without significantly increasing the number of incidental findings identified.

Keywords: stroke, diagnostic yield, neuroimaging, emergency department, CT

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Authors: Heshalini Rajagopal, Li Sze Chow, Raveendran Paramesran

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Magnetic Resonance Imaging (MRI) is one of the most important medical imaging modality. Subjective assessment of the image quality is regarded as the gold standard to evaluate MR images. In this study, a database of 210 MR images which contains ten reference images and 200 distorted images is presented. The reference images were distorted with four types of distortions: Rician Noise, Gaussian White Noise, Gaussian Blur and DCT compression. The 210 images were assessed by ten subjects. The subjective scores were presented in Difference Mean Opinion Score (DMOS). The DMOS values were compared with four FR-IQA metrics. We have used Pearson Linear Coefficient (PLCC) and Spearman Rank Order Correlation Coefficient (SROCC) to validate the DMOS values. The high correlation values of PLCC and SROCC shows that the DMOS values are close to the objective FR-IQA metrics.

Keywords: medical resonance (MR) images, difference mean opinion score (DMOS), full reference image quality assessment (FR-IQA)

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Authors: Ghazanfar Ali, Fahad N Almajhdi

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This study provides data on the viral diagnosis and molecular epidemiology of influenza A(H3N2) virus isolated in Riyadh, Saudi Arabia. Nasopharyngeal aspirates from 80 clinically infected patients in the peak of the 2010-2011 winter seasons were processed for viral diagnosis by RT-PCR. Sequencing of entire HA and NA genes of representative isolates and molecular epidemiological analysis were performed. A total of 06 patients were positive for influenza A, B and respiratory syncytial viruses by RT-PCR assays; out of these only one sample was positive for influenza A(H3N2) by RT-PCR. Phylogenetic analysis of the HA and NA gene sequences showed identities higher than 99-98.8 % in both genes. They were also similar to reference isolates in HA sequences (99 % identity) and in NA sequences (99 % identity). Amino acid sequences predicted for the HA gene were highly identical to reference strains. The NA amino acid substitutions identified did not include the oseltamivir-resistant H275Y substitution. Conclusion: Viral isolation and RT-PCR together were useful for diagnosis of the influenza A (H3N2) virus. Variations in HA and NA sequences are similar to those identified in worldwide reference isolates and no drug resistance was found.

Keywords: influenza A (H3N2), genetic characterization, viral isolation, RT-PCR, Saudi Arabia

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Authors: Leila Momenzadeh, Alexander V. Evteev, Elena V. Levchenko, Tanvir Ahmed, Irina Belova, Graeme Murch

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In this work, the phonon thermal conductivity of f.c.c. Al is investigated in detail in the temperature range 100 – 900 K within the framework of equilibrium molecular dynamics simulations making use of the Green-Kubo formalism and one of the most reliable embedded-atom method potentials. It is found that the heat current auto-correlation function of the f.c.c. Al model demonstrates a two-stage temporal decay similar to the previously observed for f.c.c Cu model. After the first stage of decay, the heat current auto-correlation function of the f.c.c. Al model demonstrates a peak in the temperature range 100-800 K. The intensity of the peak decreases as the temperature increases. At 900 K, it transforms to a shoulder. To describe the observed two-stage decay of the heat current auto-correlation function of the f.c.c. Al model, we employ decomposition model recently developed for phonon-mediated thermal transport in a monoatomic lattice. We found that the electronic contribution to the total thermal conductivity of f.c.c. Al dominates over the whole studied temperature range. However, the phonon contribution to the total thermal conductivity of f.c.c. Al increases as temperature decreases. It is about 1.05% at 900 K and about 12.5% at 100 K.

Keywords: aluminum, gGreen-Kubo formalism, molecular dynamics, phonon thermal conductivity

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Authors: Reema K. AlEssa, Sahar Alshomer, Abdullah Alfaleh, Sultan ALkhenaizan, Mohammed Albalwi

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Ichthyosis is a disorder of abnormal keratinization, characterized by excessive scaling, and consists of more than twenty subtypes varied in severity, mode of inheritance, and the genes involved. There is insufficient data in the literature about the epidemiology and characteristics of ichthyosis locally. Our aim is to identify the histopathological features and genetic profile of ichthyosis. Method: It is an observational retrospective case series study conducted in March 2020, included all patients who were diagnosed with Ichthyosis and confirmed by histological and molecular findings over the last 20 years in King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. Molecular analysis was performed by testing genomic DNA and checking genetic variations using the AmpliSeq panel. All disease-causing variants were checked against HGMD, ClinVar, Genome Aggregation Database (gnomAD), and Exome Aggregation Consortium (ExAC) databases. Result: A total of 60 cases of Ichthyosis were identified with a mean age of 13 ± 9.2. There is an almost equal distribution between female patients 29 (48%) and males 31 (52%). The majority of them were Saudis, 94%. More than half of patients presented with general scaling 33 (55%), followed by dryness and coarse skin 19 (31.6%) and hyperlinearity 5 (8.33%). Family history and history of consanguinity were seen in 26 (43.3% ), 13 (22%), respectively. History of colloidal babies was found in 6 (10%) cases of ichthyosis. The most frequent genes were ALOX12B, ALOXE3, CERS3, CYP4F22, DOLK, FLG2, GJB2, PNPLA1, SLC27A4, SPINK5, STS, SUMF1, TGM1, TGM5, VPS33B. Most frequent variations were detected in CYP4F22 in 16 cases (26.6%) followed by ALOXE3 6 (10%) and STS 6 (10%) then TGM1 5 (8.3) and ALOX12B 5 (8.3). The analysis of molecular genetic identified 23 different genetic variations in the genes of ichthyosis, of which 13 were novel mutations. Homozygous mutations were detected in the majority of ichthyosis cases, 54 (90%), and only 1 case was heterozygous. Few cases, 4 (6.6%) had an unknown type of ichthyosis with a negative genetic result. Conclusion: 13 novel mutations were discovered. Also, about half of ichthyosis patients had a positive history of consanguinity.

Keywords: ichthyosis, genetic profile, molecular characterization, congenital ichthyosis

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Authors: Ava Zarif Sanayei, Sedigheh Sina

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Despite the advancement of radiation-free interventions in the gastrointestinal and hepatobiliary fields, endoscopy and endoscopic retrograde cholangiopancreatography (ERCP) remain indispensable procedures that necessitate radiation exposure. ERCP, in particular, relies heavily on radiation-guided imaging to ensure precise delivery of therapy. Meanwhile, interventional radiology (IR) procedures also utilize imaging modalities like X-rays and CT scans to guide therapy, often under local anesthesia via small needle insertion. However, the complexity of these procedures raises concerns about radiation exposure to healthcare professionals, including nurses, who play a crucial role in these interventions. This study aims to assess the radiation exposure to the hands and fingers of nurses 1 and 2, who are directly involved in ERCP procedures utilizing (TLD-100) dosimeters at the Gastrointestinal Endoscopy department of a clinic in Shiraz, Iran. The dosimeters were initially calibrated using various phantoms and then a group was prepared and used over a two-month period. For personal equivalent dose measurement, two TLD chips were mounted on a finger ring to monitor exposure to the hands and fingers. Upon completion of the monitoring period, the TLDs were analyzed using a TLD reader, showing that Nurse 1 received an equivalent dose of 298.26 µSv and Nurse 2 received an equivalent dose of 195.39 µSv. The investigation revealed that the total radiation exposure to the nurses did not exceed the annual limit for occupational exposure. Nevertheless, it is essential to prioritize radiation protection measures to prevent potential harm. The study showed that positioning staff members and placing two nurses in a specific location contributed to somehow equal doses. To reduce exposure further, we suggest providing education and training on radiation safety principles, particularly for technologists.

Keywords: dose measurement, ERCP, interventional radiology, medical imaging

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Authors: Sean Paulsen, Michael Casey

Abstract:

In this work we present a self-supervised pretraining framework for transformers on functional Magnetic Resonance Imaging (fMRI) data. First, we pretrain our architecture on two self-supervised tasks simultaneously to teach the model a general understanding of the temporal and spatial dynamics of human auditory cortex during music listening. Our pretraining results are the first to suggest a synergistic effect of multitask training on fMRI data. Second, we finetune the pretrained models and train additional fresh models on a supervised fMRI classification task. We observe significantly improved accuracy on held-out runs with the finetuned models, which demonstrates the ability of our pretraining tasks to facilitate transfer learning. This work contributes to the growing body of literature on transformer architectures for pretraining and transfer learning with fMRI data, and serves as a proof of concept for our pretraining tasks and multitask pretraining on fMRI data.

Keywords: transfer learning, fMRI, self-supervised, brain decoding, transformer, multitask training

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