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Park, Hang-Soo, Rishi Man Chugh, Amro Elsharoud, Mara Ulin, Sahar Esfandyari, Alshimaa Aboalsoud, Lale Bakir, and Ayman Al-Hendy. "Safety of Intraovarian Injection of Human Mesenchymal Stem Cells in a Premature Ovarian Insufficiency Mouse Model." Cell Transplantation 30 (January 1, 2021): 096368972098850. http://dx.doi.org/10.1177/0963689720988502.
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Primary ovarian insufficiency (POI), a condition in which there is a loss of ovarian function before the age of 40 years, leads to amenorrhea and infertility. In our previously published studies, we demonstrated recovery of POI, correction of serum sex hormone levels, increase in the granulosa cell population, and restoration of fertility in a chemotherapy-induced POI mouse model after intraovarian transplantation of human bone marrow-derived mesenchymal stem cells (hBM-MSCs). While hBM-MSC may be a promising cell source for treatment of POI, there are few reports on the safety of stem cell-based therapy for POI. For future clinical applications, the safety of allogenic hBM-MSCs for the treatment of POI through intraovarian engraftment needs to be addressed and verified in appropriate preclinical models. In this study, we induced POI in C57/BL6 mice using chemotherapy, then treated the mice with hBM-MSCs (500,000 cells/ovary) by intraovarian injection. After hBM-MSC treatment, we analyzed the migration of engrafted cells by genomic DNA polymerase chain reaction (PCR) using a human-specific ALU repeat and by whole-body sectioning on a cryo-imaging system. We examined the possibility of transfer of human DNA from the hBM-MSCs to the resulting offspring, and compared the growth rate of offspring to that of normal mice and hBM-MSC-treated mice. We found that engrafted hBM-MSCs were detected only in mouse ovaries and did not migrate into any other major organs including the heart, lungs, and liver. Further, we found that no human DNA was transferred into the fetus. Interestingly, the engrafted cells gradually decreased in number and had mostly disappeared after 4 weeks. Our study demonstrates that intraovarian transplantation of hBM-MSCs could be a safe stem cell-based therapy to restore fertility in POI patients.
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SUWANNATA, NATTAWOOT, and APIRAT SIRITARATIWAT. "ELECTROSTATIC DISCHARGE EFFECTS ON GMR RECORDING HEADS USING A WAVELET TRANSFORM APPROACH." International Journal of Modern Physics B 23, no. 17 (July 10, 2009): 3567–72. http://dx.doi.org/10.1142/s0217979209062980.
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Electrostatic Discharge (ESD) effects have been identified as one of the most dangerous causes of giant magnetoresistive (GMR) recording head damage. These phenomena have been studied at all levels of hard-disk drive manufacturing 1. The head gimbal assembly (HGA) is mainly studied because of its exposure to the environment. The standard models are typically based on the human body model (HBM), the machine model (MM) and the charged device model (CDM) where research and practical tests are incompatible. In production, one or more ESD models are normally effective while the other is undergone under a separate model. In addition, tests in the time domain are more accurate than those in the frequency domain. However, picosecond measurements are taken with difficulty where the frequency domain measurement provides non-real time results. Therefore, this is the first report of serial ESD detection using the new technique of wavelet transform. It has been found that the glitch occurs when the ESD level of HBM – MM and HBM – CDM serial ESD on GMR heads are in the ranges of 1.2-2.6 V and 12-15 V respectively.
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Song, Biruo, Zhiguo Li, Xin Wang, Xiang Fu, Fei Liu, Lei Jin, and Zongliang Huo. "Analysis of HBM Failure in 3D NAND Flash Memory." Electronics 11, no. 6 (March 18, 2022): 944. http://dx.doi.org/10.3390/electronics11060944.
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Electrostatic discharge (ESD) events are the main factors impacting the reliability of NAND Flash memory. The behavior of human body model (HBM) failure and the corresponding physical mechanism of 3D NAND Flash memory are investigated in this paper. A catastrophic burn-out failure during HBM zapping is first presented. Analysis shows that NMOS fingers’ local heating induced by inhomogeneous substrate resistance Rsub and local heating induced by the drain contact and 3D stacked IC (SIC) structure lead to the failure. Therefore, a new approach is proposed to reduce local heat generation. Finally, by increasing N+ length (NPL) and introducing a novel contact strip, the silicon result shows enhanced ESD robustness.
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Jutong, N., D. Sompongse, P. Rakpongsiri, and Apirat Siritaratiwat. "Dependence of Flex on Suspension Capacitance on Human-Body-Model-Electrostatic-Discharge Affected TMR Head." Solid State Phenomena 152-153 (April 2009): 439–42. http://dx.doi.org/10.4028/www.scientific.net/ssp.152-153.439.
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Electrostatic discharge (ESD) effects on GMR recording heads have been reported as the major cause of head failure. Since the information density in hard-disk drives has dramatically increased, the GMR head will be no longer used. The tunneling magnetoresistive (TMR) read heads are initially introduced for a 100 Gbit/in2 density or more. Although the failure mechanism of ESD in GMR recording head has not been explicitly understood in detail, study to protect from this effect has to be undergone. As the TMR head has been commercially started, the ESD effect is closely watched. This is the first time report of the TMR equivalent circuit in order to evaluate the ESD effect. A standard human body model (HBM) is discharged across R+ and R- where the capacitance of flex on suspension (FOS) is varied. It is intriguingly found that the electrical characteristic of the TMR head during discharge period depends on discharge position. This may be explained in terms of asymmetry impedance of TMR by using adapted Thevenin’s theory. The effect of FOS component on TMR recording head is also discussed.
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Kremen, Thomas J., Tina Stefanovic, Wafa Tawackoli, Khosrowdad Salehi, Pablo Avalos, Derek Reichel, Manuel J. Perez, Juliane D. Glaeser, and Dmitriy Sheyn. "A Translational Porcine Model for Human Cell–Based Therapies in the Treatment of Posttraumatic Osteoarthritis After Anterior Cruciate Ligament Injury." American Journal of Sports Medicine 48, no. 12 (September 14, 2020): 3002–12. http://dx.doi.org/10.1177/0363546520952353.
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Background: There is a high incidence of posttraumatic osteoarthritis (PTOA) after anterior cruciate ligament (ACL) injury, and these injuries represent an enormous health care economic burden. In an effort to address this unmet clinical need, there has been increasing interest in cell-based therapies. Purpose: To establish a translational large animal model of PTOA and demonstrate the feasibility of intra-articular human cell–based interventions. Study Design: Descriptive laboratory study. Methods: Nine Yucatan mini-pigs underwent unilateral ACL transection and were monitored for up to 12 weeks after injury. Interleukin 1 beta (IL-1β) levels and collagen breakdown were evaluated longitudinally using enzyme-linked immunosorbent assays of synovial fluid, serum, and urine. Animals were euthanized at 4 weeks (n = 3) or 12 weeks (n = 3) after injury, and injured and uninjured limbs underwent magnetic resonance imaging (MRI) and histologic analysis. At 2 days after ACL injury, an additional 3 animals received an intra-articular injection of 107 human bone marrow–derived mesenchymal stem cells (hBM-MSCs) combined with a fibrin carrier. These cells were labeled with the luciferase reporter gene (hBM-MSCs-Luc) as well as fluorescent markers and intracellular iron nanoparticles. These animals were euthanized on day 0 (n = 1) or day 14 (n = 2) after injection. hBM-MSC-Luc viability and localization were assessed using ex vivo bioluminescence imaging, fluorescence imaging, and MRI. Results: PTOA was detected as early as 4 weeks after injury. At 12 weeks after injury, osteoarthritis could be detected grossly as well as on histologic analysis. Synovial fluid analysis showed elevation of IL-1β shortly after ACL injury, with subsequent resolution by 2 weeks after injury. Collagen type II protein fragments were elevated in the synovial fluid and serum after injury. hBM-MSCs-Luc were detected immediately after injection and at 2 weeks after injection using fluorescence imaging, MRI, and bioluminescence imaging. Conclusion: This study demonstrates the feasibility of reproducing the chondral changes, intra-articular cytokine alterations, and body fluid biomarker findings consistent with PTOA after ACL injury in a large animal model. Furthermore, we have demonstrated the ability of hBM-MSCs to survive and express transgene within the knee joint of porcine hosts without immunosuppression for at least 2 weeks. Clinical Relevance: This model holds great potential to significantly contribute to investigations focused on the development of cell-based therapies for human ACL injury–associated PTOA in the future (see Appendix Figure A1 , available online).
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Chen, Shen Li, and Chien Chin Tseng. "The SCR Protection Circuit Evaluation in HV DEMOS Devices." Applied Mechanics and Materials 256-259 (December 2012): 2923–26. http://dx.doi.org/10.4028/www.scientific.net/amm.256-259.2923.
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The electrostatic discharge (ESD) failure of power drain-extended MOS (DEMOS) devices, the protection circuit SCR, and a DEMOS with SCR protection circuit will be investigated in this paper. The ESD immunity of the DEMOS was very poor under the human-body model (HBM) testing. Here we discuss how to design an ESD good SCR device. Eventually, the ESD immunity of DEMOS test sample with an SCR circuit can significantly improve device ESD performance.
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Chen, Shen Li, and Chien Chin Tseng. "The SCR Protection Circuit Evaluation in HV DEMOS Devices." Advanced Materials Research 614-615 (December 2012): 1438–41. http://dx.doi.org/10.4028/www.scientific.net/amr.614-615.1438.
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The electrostatic discharge (ESD) failure of power drain-extended MOS (DEMOS) devices, the protection circuit SCR, and a DEMOS with SCR protection circuit will be investigated in this paper. The ESD immunity of the DEMOS was very poor under the human-body model (HBM) testing. Here we discuss how to design an ESD good SCR device. Eventually, the ESD immunity of DEMOS test sample with an SCR circuit can significantly improve device ESD performance.
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Putra, I. Putu A., Johan Iraeus, Fusako Sato, Mats Y. Svensson, Astrid Linder, and Robert Thomson. "Optimization of Female Head–Neck Model with Active Reflexive Cervical Muscles in Low Severity Rear Impact Collisions." Annals of Biomedical Engineering 49, no. 1 (April 24, 2020): 115–28. http://dx.doi.org/10.1007/s10439-020-02512-1.
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AbstractViVA Open Human Body Model (HBM) is an open-source human body model that was developed to fill the gap of currently available models that lacked the average female size. In this study, the head–neck model of ViVA OpenHBM was further developed by adding active muscle controllers for the cervical muscles to represent the human neck muscle reflex system as studies have shown that cervical muscles influence head–neck kinematics during impacts. The muscle controller was calibrated by conducting optimization-based parameter identification of published-volunteer data. The effects of different calibration objectives to head–neck kinematics were analyzed and compared. In general, a model with active neck muscles improved the head–neck kinematics agreement with volunteer responses. The current study highlights the importance of including active muscle response to mimic the volunteer’s kinematics. A simple PD controller has found to be able to represent the behavior of the neck muscle reflex system. The optimum gains that defined the muscle controllers in the present study were able to be identified using optimizations. The present study provides a basis for describing an active muscle controller that can be used in future studies to investigate whiplash injuries in rear impacts
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Franell, E., S. Drueen, H. Gossner, and D. Schmitt-Landsiedel. "ESD full chip simulation: HBM and CDM requirements and simulation approach." Advances in Radio Science 6 (May 26, 2008): 245–51. http://dx.doi.org/10.5194/ars-6-245-2008.
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Abstract. Verification of ESD safety on full chip level is a major challenge for IC design. Especially phenomena with their origin in the overall product setup are posing a hurdle on the way to ESD safe products. For stress according to the Charged Device Model (CDM), a stumbling stone for a simulation based analysis is the complex current distribution among a huge number of internal nodes leading to hardly predictable voltage drops inside the circuits. This paper describes an methodology for Human Body Model (HBM) simulations with an improved ESD-failure coverage and a novel methodology to replace capacitive nodes within a resistive network by current sources for CDM simulation. This enables a highly efficient DC simulation clearly marking CDM relevant design weaknesses allowing for application of this software both during product development and for product verification.
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Unnikrishnan, Kavita, Avireni Srinivasulu, and Surada Musala. "Power Rail ESD Protection Design Methodology Using Voltage-Gain Inverter Based Feedback Technology." ECS Transactions 107, no. 1 (April 24, 2022): 19385–94. http://dx.doi.org/10.1149/10701.19385ecst.
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In power rail, electrostatic discharge (ESD) is one of the assured issues to be faced. This paper intended to have a voltage gain inverter-based response technology for power rail ESD protection. This paper proposes a power MOSFET to discharge ESD current with 10 ns RC time constant for triggering and transmission gate based clamp is to keep it on until ESD event, which is 28% more efficient than the conventional clamp. The proposed clamp can endure 4500V of HBM (Human Body Model) pulse and also suitable for Charged-Device Model (CDM) protection. Here, LTspice software is used to check out the ESD performance of the transmission gate-based clamp.
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Suzuki, K., T. Muranoi, R. Sugita, M. Takeuchi, and T. Hariu. "Problems of the human body model and electrostatic discharge part 2: the HBM test for non-wired pins of LSIs." Semiconductor Science and Technology 13, no. 9 (September 1, 1998): 972–75. http://dx.doi.org/10.1088/0268-1242/13/9/002.
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Roopnarine, Aaron, and Sean A. Rocke. "Stochastic Bioimpedance-Based Channel Model of the Human Body for Galvanic Coupling." Journal of Electrical Bioimpedance 12, no. 1 (January 1, 2021): 117–24. http://dx.doi.org/10.2478/joeb-2021-0014.
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Abstract Human body communication (HBC) uses the human body as the channel to transfer data. Extensive work has been done to characterize the human body channel for different HBC techniques and scenarios. However, statistical channel bioimpedance characterisation of human body channels, particularly under dynamic conditions, remains relatively understudied. This paper develops a stochastic fading bioimpedance model for the human body channel using Monte Carlo simulations. Differential body segments were modelled as 2-port networks using ABCD parameters which are functions of bioimpedance based body parameters modelled as random variables. The channel was then modelled as the cascade of these random 2-port networks for different combinations of probability distribution functions (PDFs) assumed for the bioimpedance-based body parameters. The resultant distribution of the cascaded body segments varied for the different assumed bioimpedance based body parameter distributions and differential body segment sizes. However, considering the distribution names that demonstrated a best fit (in the top 3 PDF rankings) with highest frequency under the varying conditions, this paper recommends the distribution names: Generalized Pareto for phase distributions and Log-normal for magnitude distributions for each element in the overall cascaded random variable ABCD matrix.
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Zhao, Jian Feng, Xi Mei Chen, Bo Dong Liang, and Qiu Xia Chen. "A Review on Human Body Communication: Signal Propagation Model, Communication Performance, and Experimental Issues." Wireless Communications and Mobile Computing 2017 (October 22, 2017): 1–15. http://dx.doi.org/10.1155/2017/5842310.
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Human body communication (HBC), which uses the human body tissue as the transmission medium to transmit health informatics, serves as a promising physical layer solution for the body area network (BAN). The human centric nature of HBC offers an innovative method to transfer the healthcare data, whose transmission requires low interference and reliable data link. Therefore, the deployment of HBC system obtaining good communication performance is required. In this regard, a tutorial review on the important issues related to HBC data transmission such as signal propagation model, channel characteristics, communication performance, and experimental considerations is conducted. In this work, the development of HBC and its first attempts are firstly reviewed. Then a survey on the signal propagation models is introduced. Based on these models, the channel characteristics are summarized; the communication performance and selection of transmission parameters are also investigated. Moreover, the experimental issues, such as electrodes and grounding strategies, are also discussed. Finally, the recommended future studies are provided.
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Piqueras, Ana, Bengt Pipkorn, Johan Iraeus, Mario Maza-Frechín, and Francisco J. López-Valdés. "Assessment of in situ chest deflection of post mortem human subjects (PMHS) and personalized human body models (HBM) in nearside oblique impacts." Traffic Injury Prevention 23, no. 4 (February 24, 2022): 181–86. http://dx.doi.org/10.1080/15389588.2022.2036731.
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Chen, Shen-Li, Pei-Lin Wu, and Yu-Jen Chen. "Robust ESD-Reliability Design of 300-V Power N-Channel LDMOSs with the Elliptical Cylinder Super-Junctions in the Drain Side." Electronics 9, no. 5 (April 29, 2020): 730. http://dx.doi.org/10.3390/electronics9050730.
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The weak ESD-immunity problem has been deeply persecuted in ultra high-voltage (UHV) metal-oxide-semiconductor field-effect transistors (MOSFETs) and urgently needs to be solved. In this paper, a UHV 300 V circular n-channel (n) lateral diffused MOSFET (nLDMOS) is taken as the benchmarked reference device for the electrostatic discharge (ESD) capability improvement. However, a super-junction (SJ) structure in the drain region will cause extra depletion zones in the long drain region and reduce the peak value of the channel electric field. Therefore, it may directly increase the resistance of the device to ESD. Then, in this reformation project for UHV nLDMOSs to ESD, two strengthening methods were used. Firstly, the SJ area ratio changed by the symmetric eight-zone elliptical-cylinder length (X) variance (i.e., X = 5, 10, 15 and 20 μm) is added into the drift region of drain side to explore the influence on ESD reliability. From the experimental results, it could be found that the breakdown voltages (VBK) were changed slightly after adding this SJ structure. The VBK values are filled between 391 and 393.5 V. Initially, the original reference sample is 393 V; the VBK changing does not exceed 0.51%, which means that these components can be regarded as little changing in the conduction characteristic after adding these SJ structures under the normal operating conditions. In addition, in the ESD transient high-voltage bombardment situation, the human-body model (HBM) capability of the original reference device is 2500 V. Additionally, as SJs with the length X high-voltage P-type well (HVPW) are inserted into the drain-side drift region, the HBM robustness of these UHV nLDMOSs increases with the length X of the HVPW. When the length X (HVPW) is 20 μm, the HBM value can be upgraded to a maximum value of 5500 V, the ESD capability is increased by 120%. A linear relationship between the HBM immunity level and area ratio of SJs in the drains side in this work can be extracted. The second part revealed that, in the symmetric four-zone elliptical cylinder SJ modulation, the HBM robustness is generally promoted with the increase of HVPW SJ numbers (the highest HBM value (4500 V) of the M5 device improved by 80% as compared with the reference device under test (DUT)). Therefore, from this work, we can conclude that the addition of symmetric elliptical-cylinder SJ structures into the drain-side drift region of a UHV nLDMOS is a good strategy for improving the ESD immunity.
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Muramatsu, Dairoku, and Ken Sasaki. "Transmission Analysis in Human Body Communication for Head-Mounted Wearable Devices." Electronics 10, no. 10 (May 19, 2021): 1213. http://dx.doi.org/10.3390/electronics10101213.
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As society ages, wireless body area networks (WBANs) are expected to increasingly improve the quality of life of the elderly and disabled. One promising WBAN technology is human body communication (HBC), which utilizes part of the human body as a transmission medium. Communication between head-mounted wearable devices, such as hearing aids, is a potential HBC application. To clarify the HBC transmission mechanism between head-mounted wearable devices, this study analyzes the input impedance characteristics of the transceiver electrodes, transmission characteristics, and electric field distributions around and through a detailed head model. The investigation was performed via an electromagnetic field simulation. The signal frequency had less effect on the transmission characteristics and electric field distributions at 10, 20, and 30 MHz. However, the transmission mechanism between the head-mounted wearable devices was influenced by the number of electrodes in the transceiver. Moreover, the transmission characteristics between two-electrode transceivers were improved by impedance matching. Finally, the availability of the proposed system was evaluated from power consumption and human safety perspectives.
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Godhavari, T., and D. Urvasi. "Biotelemetry Using Human Area Networking." International Journal of Engineering & Technology 7, no. 3.27 (August 15, 2018): 352. http://dx.doi.org/10.14419/ijet.v7i3.27.17971.
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Human Body Communication (HBC) is a novel communication method between devices which use human body as a transmission medium. This idea is mostly based on the concept of wireless biomedical monitoring system. The on-body sensor nodes can monitor vital signs of a human body and use the body as a transmission medium. This technology is convenient for long durations of clinical monitoring with the option of more mobility and freedom for the user. Biotelemetry is remote monitoring, measuring and recording of a living organism’s function, activity or condition. Network of sensor nodes placed on or implanted inside the body of a subject is called Human Body Area Network (HAN). RedTacton is a user-friendly pervasive technology that establishes a communication between human body and devices in a closer proximity. This paper proclaims model of a human area networking technologies that enables communication by means of “Touching”. Redtacton technology was implemented to overcome the weak radio signals, data speeds and security –risks on unwanted signal interceptions. Here, human body is the transmitting medium supporting IEEE 802.3 half-duplex communication at 10 Mbits/s. RedTacton uses the minute electric field generated by human body as a medium to transmit the data.
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Muramatsu, Dairoku, and Ken Sasaki. "Input Impedance Analysis of Wearable Antenna and Experimental Study with Real Human Subjects: Differences between Individual Users." Electronics 10, no. 10 (May 12, 2021): 1152. http://dx.doi.org/10.3390/electronics10101152.
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In human body communication (HBC) systems, radio-frequency signals are excited in the human body through a wearable antenna comprised of electrodes that are in contact with the surface of the body. The input impedance characteristics of these antennas are important design parameters for increasing transmission efficiency and reducing signal reflection, similar to other wireless circuits. In this study, we discuss variations of input impedance characteristics of a wearable antenna prototype caused by differences among real human subjects. A realistic human arm model is used for simulations, and the analytical results obtained are compared to measured data obtained from real human subjects, in a range from 1 to 100 MHz. The simulations of input impedance characteristics from antennas worn on the wrists of male and female models with dry and wet skin conditions show that the impedance variation between genders is small. The moisture condition of the skin has little influence on frequencies exceeding several MHz. Measurements with a proto-type wearable antenna and 22 real human subjects reveal that HBC is robust against the variations of individual users from the viewpoint of the voltage standing wave ratio. Moreover, a simplified rectangular prism model is proposed to analyze the thickness of body tissues. Comparisons of measured input impedances indicate that individual differences in impedance are mainly due to differences in the thickness of skin and fat layers. The model also enables us to design the antenna prototype without multiple subject experiments.
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Humbert, Olivier, and Hans-Peter Kiem. "Long-Term Increase in Fetal Hemoglobin Expression in Nonhuman Primates Following Transplantation of Autologous Bcl11a Nuclease-Edited HSCs." Blood 126, no. 23 (December 3, 2015): 2035. http://dx.doi.org/10.1182/blood.v126.23.2035.2035.
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Abstract Elevated levels of fetal hemoglobin (HbF) ameliorate the clinical symptoms of beta-thalassemia and sickle cell anemia. The transcription factor B-cell lymphoma/leukemia 11A (BCL11A) is required for silencing of gamma-globin expression in adult erythroid cells and functions as a switch from fetal to adult hemoglobin production in humans. BCL11A therefore constitutes a therapeutic target for the treatment of hemoglobinopathies. We inactivated BCL11A function by double-strand DNA break-induced mutagenesis using Transcription Activator-Like Effector Nucleases (TALENs). 20 to 30% gene editing could be achieved in vitro in human and nonhuman primate CD34+ cells by TALEN mRNAs electroporation targeting exon 2 of Bcl11a. Colony-forming efficiency was slightly lower in Bcl11a-edited CD34+ cells but lineage differentiation potential was unchanged. Erythroid differentiation of CD34+ cells in culture showed increased Fetal to Beta hemoglobin ratio in both human and primate Bcl11a-modified cells as compared to control cells, thus validating our editing approach to increase HbF production. To determine if Bcl11a-edited hematopoietic stem cells (HSCs) could be engrafted and give rise to HbF-producing erythrocytes, we transplanted a pigtail macaque with autologous CD34+ electroporated with Bcl11a TALEN mRNA following conditioning by total body irradiation. We detected about 1 % gene disruption in vivo early post-transplant and disruption frequency gradually declined to reach a set point of about 0.3% starting at day 28 post-transplantation. In this analysis, which we have so far taken out to 42 days, single clones could be tracked based on their mutation signature, and we found that several clones persisted over time, confirming engraftment of Bcl11a-modified cells. Since the transplantation procedure and chemo-radiotherapy conditioning can raise HbF production, three control animals that were transplanted using similar conditions as with the Bcl11a-edited HSCs and one untransplanted animal were also included in our analysis. Flow cytometry measurement of HbF in peripheral blood showed a rapid increase in F-cell production in all animals, reaching levels that ranged from 10% to 40% by 30 days, while the untransplanted control showed basal HbF expression of about 0.5% (Fig. 1A). The peak for HbF expression lasted for about 140 days and eventually returned to basal levels that averaged 0.5% for all control animals. In comparison, the animal transplanted with Bcl11a-edited cells showed significantly higher HbF levels starting at day 140 post-treatment (1-1.5%), and HbF production has remained constant for at least 150 days. This result was confirmed by hemoglobin mRNA analysis in peripheral blood using real-time PCR. We found a rapid increase in gamma globin expression following transplantation, before returning to near basal levels. As compared to controls, the animal transplanted with Bcl11a-edited cells showed a 5 to 10-fold increase in gamma to beta globin ratio at day 140 and this ratio has remained constant ever since (Fig. 1B). We are currently working on ways to enhance Bcl11a-editing and to select for Bcl11a-modified HSCs using targeted integration of the chemoselection cassette P140K MGMT to ultimately achieve curative HbF production. Potential TALEN off-target sites will also be examined as well as any side effect associated with the inactivation of BCL11A. Overall, our data demonstrate that transplantation of Bcl11a-edited HSCs results in elevated HbF production in nonhuman primates. Furthermore, we show that nonhuman primates can serve as a useful model for novel gene editing strategies toward the treatment of hemoglobinopathies. Figure 1. In vivo monitoring of HbF expression by flow cytometry and real-time PCR. (A) Intracellular HbF staining of peripheral blood measured by flow cytometry. (B) Real-time PCR analysis of hemoglobin transcripts in RNA isolated from peripheral blood. Expression was normalized to GAPDH and %HbG is calculated as HbG/(HbG+HbB). HbG=gamma globin; HbB=beta globin. Black line=Bcl11a transplant; grey line=control transplant; dashed line=untransplanted control. Figure 1. In vivo monitoring of HbF expression by flow cytometry and real-time PCR. (A) Intracellular HbF staining of peripheral blood measured by flow cytometry. (B) Real-time PCR analysis of hemoglobin transcripts in RNA isolated from peripheral blood. Expression was normalized to GAPDH and %HbG is calculated as HbG/(HbG+HbB). HbG=gamma globin; HbB=beta globin. Black line=Bcl11a transplant; grey line=control transplant; dashed line=untransplanted control. Disclosures No relevant conflicts of interest to declare.
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Chen, Fuxing, and Hong Hu. "Nonlinear vibration of knitted spacer fabric under harmonic excitation." Journal of Engineered Fibers and Fabrics 15 (January 2020): 155892502098356. http://dx.doi.org/10.1177/1558925020983561.
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Knitted spacer fabrics can be an alternative material to typical rubber sponges and polyurethane foams for the protection of the human body from vibration exposure, such as automotive seat cushions and anti-vibration gloves. To provide a theoretical basis for the understanding of the nonlinear vibration behavior of the mass-spacer fabric system under harmonic excitation, experimental, analytical and numerical methods are used. Different from a linear mass-spring-damper vibration model, this study builds a phenomenological model with the asymmetric elastic force and the fractional derivative damping force to describe the periodic solution of the mass-spacer fabric system under harmonic excitation. Mathematical expression of the harmonic amplitude versus frequency response curve (FRC) is obtained using the harmonic balance method (HBM) to solve the equation of motion of the system. Parameter values in the model are estimated by performing curve fit between the modeled FRC and the experimental data of acceleration transmissibility. Theoretical analysis concerning the influence of varying excitation level on the FRCs is carried out, showing that nonlinear softening resonance turns into nonlinear hardening resonance with the increase of excitation level, due to the quadratic stiffness term and the cubic stiffness term in the model, respectively. The quadratic stiffness term also results in biased vibration response and causes an even order harmonic distortion. Besides, the increase of excitation level also results in elevated peak transmissibility at resonance.
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JUTONG, NUTTACHAI, APIRAT SIRITARATIWAT, DUANGPORN SOMPONGSE, and PORNCHAI RAKPONGSIRI. "ELECTROSTATIC DISCHARGE EFFECT ON TMR RECORDING HEAD: A FLEX ON SUSPENSION CAPACITANCE APPROACH." International Journal of Modern Physics B 23, no. 17 (July 10, 2009): 3586–90. http://dx.doi.org/10.1142/s0217979209063018.
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Electrostatic discharge (ESD) effects on GMR recording heads have been reported as the major cause of head failure. Since the information density in hard-disk drives has dramatically increased, the GMR head will be no longer in use. The tunneling magnetoresistive (TMR) read heads are initially introduced for a 100 Gbit/in2 density or more. Though the failure mechanism of ESD in GMR recording heads has not been explicitly understood in detail, a study to protect from this effect has to be done. As the TMR head has been commercially started, the ESD effect must be considered. This is the first time that the TMR equivalent circuit has been reported in order to evaluate the ESD effect. A standard human body model (HBM) is discharged across R+ and R- where the capacitances of flex on suspension (FOS) are varied. It is intriguingly found that the electrical characteristics of the TMR head during the discharge period depend on the discharge position. This may be explained in terms of the asymmetry impedance of TMR by using adapted Thevenin's theory. The effect of FOS components on TMR recording heads is also discussed.
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Diez Marín, Mónica, JULIO ABAJO ALONSO, ALBERTO NEGRO MARNE, SUSANA MARIA ESCALANTE CASTRODEZA, and MARIA TERESA FERNANDEZ. "CHILD SAFETY IN AUTONOMOUS VEHICLES: "LIVING ROOM" LAYOUT." DYNA 97, no. 1 (January 1, 2022): 30–34. http://dx.doi.org/10.6036/10215.
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Autonomous vehicles start to be introduced on our roads and will soon become a reality. Although fatal traffic accidents will be significantly reduced, remaining fatal passenger car crashes should be taken into account to ensure the safety of users. The new highly adaptable interior designs, with totally different layouts from the current ones, may significantly impact occupant safety, especially child passenger safety. Analyzing how these new vehicles affect child safety is a challenge that needs to be addressed. The "living room" layout (face-to-face seating position) is one of the preferences of families traveling with children. Young children need further support and supervision so the possibility of rotating seats to be able to be in front of the small children is a valuable feature for parents. Therefore, new seating orientations away from the forward facing position should be taken into account to ensure children protection. The objective of this study is to evaluate child occupant safety in a "living room" seating position (a possible option in full autonomous vehicles) versus the current forward facing position. Virtual testing methodology was used to perform this study. The virtual PIPER child human body model (HBM) was used. This model is one of the only HBMs developed and validated from child PMHS data (Paediatric Post-Mortem Human Surrogate). The two configurations were defined according with the EuroNCAP child occupant protection test protocol. It was found that the "living room" layout presents worse results according to the child's head injury patterns than in forward facing position. In conclusion, attending to the new seating orientations away from the forward facing position, it is necessary to adapt the restraint systems; otherwise children could suffer potentially dangerous situations.
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Umar Paputungan, Lentji Rinny Ngangi, and Wapsiaty Utiah. "Factors affecting calf parturition of the Ongole grade beef heifers." Open Access Research Journal of Life Sciences 3, no. 2 (June 30, 2022): 077–82. http://dx.doi.org/10.53022/oarjls.2022.3.2.0052.
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Serious economic losses due to calf or heifer increasing mortality during parturition, the normal calving period without human interference was urgently needed. The most important internal factor influencing calving difficulty was Calf birth weight (CBW). Other external factors considered to contribute calving difficulty were heifer live weight (HLW), heifer body length (HBL), and heifer chest girth (HCG), calf parturition durability (CPD) representing linear CBW. Objective of this study was to estimate above factor mostly affecting calving difficulty of Ongole Grade heifers mated by artificial insemination method. Study was involving 126 Ongole Grade heifers at the artificial insemination center of North Sulawesi province, Indonesia. Data on HLW, HBL, HCG, CPD and CBW were collected from 126 heifers at ages of two to three years old. All linear body measurements were included as independent variables in multiple regression equation affecting dependent variable of CBW in the models using statistical datasheet of Microsoft Office Excel 2007. Results showed that HCG, HBL and CPD as independent variables can be recommended to predict CBW representing internal factor of Ongole Grade heifers in the multiple regression model as follows: Calf birth weight (Y in kg) = 26.871 + 0.0033 heifer body length (X1 in cm) – 00.0255 heifer chest girth (X2 in cm) + 0.032 calf parturition durability (X3 in minute) with determination coefficient (R2) of 0.91.
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Suzuki, Kei, Hiroyuki Nakano, Kazuya Inoue, Yoichiro Nakajima, Sho Mizobuchi, Michi Omori, Nahoko Kato-Kogoe, Katsuaki Mishima, and Takaaki Ueno. "Examination of new parameters for sex determination of mandible using Japanese computer tomography data." Dentomaxillofacial Radiology 49, no. 5 (July 2020): 20190282. http://dx.doi.org/10.1259/dmfr.20190282.
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Objective: In the field of forensic science, sex discrimination of skeletons is an important identification item for personal identification. The individual sex discrimination method using skeletons includes a determination method using measurement values and a macroscopic form observation method. Both methods have advantage and disadvantage. In this study, we used the homologous model technique and principal component (PC) analysis to determine gender difference from morphology of the mandible. Methods and materials: 45 patients (23 males and 22 females) of CT imaging for tooth extraction from January 2018 to March 2019 at department of oral surgery, Osaka Medical College. The mean age was 43.1 ± 14.6. Patients with less than 14 remaining teeth were excluded because the number of remaining teeth may affect the shape of the mandible. 3D images were constructed, and 20 landmarks plotting on the 3D model surfaces. We generated template models of the mandible consisting of approximately 8434 polygons. The template model automatically fitted into the individually scanned point cloud of the mandible by minimising external and internal energy functions. As described above, the mandibles were constructed for each sample by using the Homologous Body Modeling software (HBM, Digital Human Technology, Inc.) and the mHBM-Rugle (Medic Engineering Corporation). The mandibles were analysed using the PCA. Results: The contribution of the most important PC was found to be 27.2%. 12 PCs explained over 75% of the total variance. That is, it was able to express 75% or more of the mandible expression with 12 PCs. A significant difference between male and female was observed in the first PCs (Wilcoxon test, p < 0.05). Visualising the result of the first PC showed that the mandibular branch of male was larger than that of female, and the mandible angle was overhanging outside. Conclusion: This method is a combination of the determination method using the previous measurement values and the determination using macroscopic observation, and is considered to be innovative method.
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Nguyen, Julia, Fuad Abdulla, Chunsheng Chen, Phong Nguyen, Minh Nguyen, Benjamin Tittle, Gerard O'Sullivan, John D. Belcher, and Gregory M. Vercellotti. "Phenotypic Characterization the Townes Sickle Mice." Blood 124, no. 21 (December 6, 2014): 4916. http://dx.doi.org/10.1182/blood.v124.21.4916.4916.
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Abstract The HbSS-Townes mouse model, developed in Dr. Tim Townes laboratory, University of Alabama, Birmingham (and kindly provided by him to our laboratory) were created on a mixed genetic background in which the murine adult α-globin genes were replaced with the human α-globin gene (genotype: Hba hα/hα) and the murine adult β-globin genes were replaced with human sickle βS- and fetal Aγ-globin gene fragments linked together (genotype: Hbb hAγβS/hAγβS) (Wu LC et al. Blood 2006;108: 1183-1188). HbSS-Townes mice have anemia, a shortened RBC half-life of 2.5 days and a severe disease phenotype. Control HbAA-Townes mice were created by replacing the murine globin genes with human α-globin gene (genotype: Hba hα/hα) and linked human βA- and fetal Aγ-globins (genotype: Hbb hAγβA/hAγβA), while HbAS-Townes heterozygous mice were developed by breeding HbAA and HbSS mice. Many laboratories are utilizing these mice but complete phenotypic description of these three models has not been described including: hematology, kidney and liver function, inflammatory markers, haptoglobin and hemopexin levels, red cell half-lives, organ histopathology and vascular responses to vaso-occlusive stimuli. Table 1 summarizes our findings. There was a clear difference in histopathology between the HbSS and other groups (HbAA and HbAS). HbSS mice had hepatic necrosis, increased erythropoiesis and increased hemosiderin within the liver and some subtle lesions involving the glomeruli in the kidneys. Additional findings were a marked increase in size of spleen (7.0-7.6 x by % body weights) attributed to severe congestion and increased erythropoiesis. No lesions were observed in the lungs and other tissues. The tissues evaluated in the HbAS and HbAA groups were essentially normal. In contrast, HbSS mice had multifocal irregular areas of necrosis within the liver, with reactive leukocyte infiltrates (mainly neutrophils in the more acute lesions with a greater proportion of mononuclear cells (macrophages etc.) in more chronic lesions. MPO immunohistochemistry confirmed the presence of neutrophils in the liver. There was a substantial increase in iron (and hemosiderin) in the livers of HbSS mice, confirmed by a Prussian Perls stain and low, but detectable, levels of iron in the proximal convoluted tubules of the kidney. This is consistent with increased red cell turnover in the HbSS mice. Total iron mass in the markedly enlarged spleen is very high. There is a somewhat subtle glomerulopathy present in the kidney, with enlarged glomeruli with variable ectasia of vessels, and mesangial derangement. In conclusion the Townes mouse models provide a spectrum of severe hemolytic disease that in many ways mimic the human disease albeit imperfectly. TableTable 1 HbAAHbASHbSSHb (g/dL)12.0 ± 0.610.6 ± 0.59.5 ± 1.4*Hematocrit (%)49.6 ± 2.345.0 ± 4.2*29.2 ± 0.9*#WBC (K/µL)10.8 ± 1.213.2 ± 4.038.2 ± 4.9*#Platelet Counts (K/uL)854 ± 78889 ± 1421004 ± 179Monocytes (%)8.0 ± 1.17.6 ± 1.77.4 ± 1.0Lymphocytes (%)60 ± 3.063.8 ± 5.667.5 ± 9.1Neutrophils (%)28.6 ± 5.926.1 ± 8.727.8 ± 2.2Reticulocytes (%)7.8 ± 1.78.6 ± 4.556.8 ± 2.6*#RBC Half-Life (days)15.710.62.4Expired CO (nmoles/h/g)0.92 ± 0.241.27 ± 0.236.33 ± 1.08*Serum Bilirubin (mg/dl)3.5 ± 0.94.3 ± 0.65.6 ± 0.4*Urine Creatinine (mg/dL)44.1 ± 3.845.9 ± 3.856.2 ± 7.0*Urine Osmolality (mOsm/kg H2O)2147 ± 761707 ± 2651361 ± 32*Serum Haptoglobin (µg/ml)39.3 ± 3.80.5 ± 0.2*2.3 ± 1.4*Serum Hemopexin (µg/ml)802 ± 266169 ± 51*124 ± 35*Serum SAP (µg/ml)20.9 ± 7.214.1 ± 12.086.7 ± 20.2*#Stasis at 1h in Response to Hb (%)10.0 ± 3.219.8 ± 2.7*30.0 ± 3.4*#Mortality at 24h in Response to Heme (%)00100*#Liver % of Body Weight4.95 ± 0.484.39 ± 0.356.22 ± 0.21*#Spleen % of Body Weight0.79 ± 0.140.87 ± 0.396.61 ± 0.75*#Kidney % of Body Weight0.65 ± 0.270.72 ± 0.190.73 ± 0.24Liver Necrosis Score0.0 ± 0.00.25 ± 0.502.38 ± 0.25*Liver Fe Score0.0 ± 0.00.25 ± 0.53.0 ± 0.0*Lung Fe Score0.0 ± 0.00.0 ± 0.0*1.0 ± 0.0*#Spleen Fe Score3.0 ± 0.03.0 ± 0.02.0 ± 0.0*#Kidney Fe Score0.0 ± 0.00.25 ± 0.51.75 ± 0.5*#Liver Gr1 Score1.0 ± 0.01.25 ± 0.52.25 ± 0.5*Lung Gr1 Score1.0 ± 0.01.0 ± 0.01.25 ± 0.5Spleen Gr1 Score1.5 ± 0.62.0 ± 0.02.0 ± 0.0Kidney Gr1 Score0.25 ± 0.50.25 ± 0.50.75 ± 0.5* p<0.05 vs HbAA; # p<0.05 vs HbAS Disclosures No relevant conflicts of interest to declare.
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Sordini, Laura, João C. Silva, Fábio F. F. Garrudo, Carlos A. V. Rodrigues, Ana C. Marques, Robert J. Linhardt, Joaquim M. S. Cabral, Jorge Morgado, and Frederico Castelo Ferreira. "PEDOT:PSS-Coated Polybenzimidazole Electroconductive Nanofibers for Biomedical Applications." Polymers 13, no. 16 (August 19, 2021): 2786. http://dx.doi.org/10.3390/polym13162786.
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Bioelectricity drives several processes in the human body. The development of new materials that can deliver electrical stimuli is gaining increasing attention in the field of tissue engineering. In this work, novel, highly electrically conductive nanofibers made of poly [2,2′-m-(phenylene)-5,5′-bibenzimidazole] (PBI) have been manufactured by electrospinning and then coated with cross-linked poly (3,4-ethylenedioxythiophene) doped with poly (styrene sulfonic acid) (PEDOT:PSS) by spin coating or dip coating. These scaffolds have been characterized by scanning electron microscopy (SEM) imaging and attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy. The electrical conductivity was measured by the four-probe method at values of 28.3 S·m−1 for spin coated fibers and 147 S·m−1 for dip coated samples, which correspond, respectively, to an increase of about 105 and 106 times in relation to the electrical conductivity of PBI fibers. Human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) cultured on the produced scaffolds for one week showed high viability, typical morphology and proliferative capacity, as demonstrated by calcein fluorescence staining, 4′,6-diamidino-2-phenylindole (DAPI)/Phalloidin staining and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide] assay. Therefore, all fiber samples demonstrated biocompatibility. Overall, our findings highlight the great potential of PEDOT:PSS-coated PBI electrospun scaffolds for a wide variety of biomedical applications, including their use as reliable in vitro models to study pathologies and the development of strategies for the regeneration of electroactive tissues or in the design of new electrodes for in vivo electrical stimulation protocols.
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Ozden, Simona, Madeleine Cochet, Jacqueline Mikol, Antonio Teixeira, Antoine Gessain, and Claudine Pique. "Direct Evidence for a Chronic CD8+-T-Cell-Mediated Immune Reaction to Tax within the Muscle of a Human T-Cell Leukemia/Lymphoma Virus Type 1-Infected Patient with Sporadic Inclusion Body Myositis." Journal of Virology 78, no. 19 (October 1, 2004): 10320–27. http://dx.doi.org/10.1128/jvi.78.19.10320-10327.2004.
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ABSTRACT Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) infection can lead to the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), concomitantly with or without other inflammatory disorders such as myositis. These pathologies are considered immune-mediated diseases, and it is assumed that migration within tissues of both HTLV-1-infected CD4+ T cells and anti-HTLV-1 cytotoxic T cells represents a pivotal event. However, although HTLV-1-infected T cells were found in inflamed lesions, the antigenic specificity of coinfiltrated CD8+ T cells remains to be determined. In this study, we performed both ex vivo and in situ analyses using muscle biopsies obtained from an HTLV-1-infected patient with HAM/TSP and sporadic inclusion body myositis. We found that both HTLV-1-infected CD4+ T cells and CD8+ T cells directed to the dominant Tax antigen can be amplified from muscle cell cultures. Moreover, we were able to detect in two successive muscle biopsies both tax mRNA-positive mononuclear cells and T cells recognized by the Tax11-19/HLA-A*02 tetramer and positive for perforin. These findings provide the first direct demonstration that anti-Tax cytotoxic T cells are chronically recruited within inflamed tissues of an HTLV-1 infected patient, which validates the cytotoxic immune reaction model for the pathogenesis of HTLV-1-associated inflammatory disease.
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Rana, Rabia Mukhtar, Shailima Rampogu, Amir Zeb, Minky Son, Chanin Park, Gihwan Lee, Sanghwa Yoon, et al. "In Silico Study Probes Potential Inhibitors of Human Dihydrofolate Reductase for Cancer Therapeutics." Journal of Clinical Medicine 8, no. 2 (February 11, 2019): 233. http://dx.doi.org/10.3390/jcm8020233.
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Dihydrofolate reductase (DHFR) is an essential cellular enzyme and thereby catalyzes thereduction of dihydrofolate to tetrahydrofolate (THF). In cancer medication, inhibition of humanDHFR (hDHFR) remains a promising strategy, as it depletes THF and slows DNA synthesis and cellproliferation. In the current study, ligand-based pharmacophore modeling identified and evaluatedthe critical chemical features of hDHFR inhibitors. A pharmacophore model (Hypo1) was generatedfrom known inhibitors of DHFR with a correlation coefficient (0.94), root mean square (RMS)deviation (0.99), and total cost value (125.28). Hypo1 was comprised of four chemical features,including two hydrogen bond donors (HDB), one hydrogen bond acceptor (HBA), and onehydrophobic (HYP). Hypo1 was validated using Fischer's randomization, test set, and decoy setvalidations, employed as a 3D query in a virtual screening at Maybridge, Chembridge, Asinex,National Cancer Institute (NCI), and Zinc databases. Hypo1-retrieved compounds were filtered byan absorption, distribution, metabolism, excretion, and toxicity (ADMET) assessment test andLipinski's rule of five, where the drug-like hit compounds were identified. The hit compounds weredocked in the active site of hDHFR and compounds with Goldfitness score was greater than 44.67(docking score for the reference compound), clustering analysis, and hydrogen bond interactionswere identified. Furthermore, molecular dynamics (MD) simulation identified three compounds asthe best inhibitors of hDHFR with the lowest root mean square deviation (1.2 Å to 1.8 Å), hydrogenbond interactions with hDHFR, and low binding free energy (−127 kJ/mol to −178 kJ/mol). Finally,the toxicity prediction by computer (TOPKAT) affirmed the safety of the novel inhibitors of hDHFRin human body. Overall, we recommend novel hit compounds of hDHFR for cancer and rheumatoidarthritis chemotherapeutics.
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Kim, Su Yeong, and Dae Yong Yi. "Components of human breast milk: from macronutrient to microbiome and microRNA." Clinical and Experimental Pediatrics 63, no. 8 (August 15, 2020): 301–9. http://dx.doi.org/10.3345/cep.2020.00059.
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Human breast milk (HBM) is essential for the infant’s growth and development right after birth and is an irreplaceable source of nutrition for early human survival. Various infant formulas have many similarities to HBM in many components, but there is no perfect substitute for HBM. Recently, various breast milk components and their roles have been studied according to the development of various analysis techniques. As is already well known, HBM contains about 87%–88% water, and 124- g/L solid components as macronutrients, including about 7% (60–70 g/L) carbohydrates, 1% (8–10 g/L) protein, and 3.8% (35–40 g/L) fat. The composition may vary depending on the environmental factors, including maternal diet. Colostrum is low in fat but high in protein and relatively rich in immuneprotective components. Although HBM contains enough vitamins to ensure normal growth of the infant, vitamins D and K may be insufficient, and the infant may require their supplementation. Growth factors in HBM also serve as various bioactive proteins and peptides on the intestinal tract, vasculature, nervous system, and endocrine system. In the past, HBM of a healthy mother was thought to be sterile. However, several subsequent studies have confirmed the presence of rich and diverse microbial communities in HBM. Some studies suggested that the genera <i>Staphylococcus</i> and <i>Streptococcus</i> may be universally predominant in HBM, but the origin of microbiota still remains controversial. Lastly, milk is the one of most abundant body fluid of microRNAs, which are known to play a role in various functions, such as immunoprotection and developmental programming, through delivering from HBM and absorption by intestinal epithelial cells. In conclusion, HBM is the most important source of nutrition for infants and includes microbiomes and miRNAs for growth, development, and immunity.
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Cecchetto, Cinzia, Florian Ph S. Fischmeister, Sarah Gorkiewicz, Wolfgang Schuehly, Deepika Bagga, Valentina Parma, and Veronika Schöpf. "Human body odor increases familiarity for faces during encoding‐retrieval task." Human Brain Mapping 41, no. 7 (January 6, 2020): 1904–19. http://dx.doi.org/10.1002/hbm.24920.
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Shin, Tae Hwan, Geetika Phukan, Jeom Soon Shim, Duc-Toan Nguyen, Yongman Kim, Justin D. Oh-Lee, Hyeon-Seong Lee, Man Jeong Paik, and Gwang Lee. "Restoration of Polyamine Metabolic Patterns inIn VivoandIn VitroModel of Ischemic Stroke following Human Mesenchymal Stem Cell Treatment." Stem Cells International 2016 (2016): 1–11. http://dx.doi.org/10.1155/2016/4612531.
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We investigated changes in PA levels by the treatment of human bone-marrow-derived mesenchymal stem cells (hBM-MSCs) in ischemic stroke in rat brain model and in cultured neuronal SH-SY5Y cells exposed to oxygen-glucose deprivation (OGD). In ischemic rat model, transient middle cerebral artery occlusion (MCAo) was performed for 2 h, followed by intravenous transplantation of hBM-MSCs or phosphate-buffered saline (PBS) the day following MCAo. Metabolic profiling analysis of PAs was examined in brains from three groups: control rats, PBS-treated MCAo rats (MCAo), and hBM-MSCs-treated MCAo rats (MCAo + hBM-MSCs). In ischemic cell model, SH-SY5Y cells were exposed to OGD for 24 h, treated with hBM-MSCs (OGD + hBM-MSCs) prior to continued aerobic incubation, and then samples were collected after coculture for 72 h. In thein vivoMCAo ischemic model, levels of some PAs in brain samples of the MCAo and MCAo + hBM-MSCs groups were significantly different from those of the control group. In particular, putrescine, cadaverine, and spermidine in brain tissues of the MCAo + hBM-MSCs group were significantly reduced in comparison to those in the MCAo group. In thein vitroOGD system,N1-acetylspermidine, spermidine,N1-acetylspermine, and spermine in cells of the OGD + hBM-MSCs group were significantly reduced compared to those of OGD group.
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Cui, Shuaiying, Jose Sangerman, Seyed Mehdi Nouraie, Yan Dai, Oluwakemi Owoyemi, Robert E. Taylor, and Susan P. Perrine. "Activity of RN-1, an LSD-1 Inhibitor, on Fetal Globin Expression in Sickle Mice and Sickle Erythroid Progenitors." Blood 126, no. 23 (December 3, 2015): 961. http://dx.doi.org/10.1182/blood.v126.23.961.961.
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Abstract Sickle cell disease (SCD) is the most common monogenic disorder, afflicting millions worldwide, and causing hemolytic anemia and chronic organ damage from vaso-occlusion. Fetal hemoglobin (HbF) is an endogenous type of hemoglobin present in all humans during development, which is normally suppressed in infancy. Biochemical and clinical studies have shown that increased synthesis of HbF inhibits sickle hemoglobin (HbS) polymerization and reduces clinical severity. Concerted efforts have been made to induce the synthesis of HbF in adult erythroid cells with chemical inducers of HbF and through disruption of transcription factors in repressor complexes. As wide variability in individual responses to drug candidates have been observed in clinical trials, consistently effective HbF inducers are highly desired. We previously identified that Lysine-specific histone demethylase 1 (LSD1) is involved in the regulation of the fetal γ-globin genes, and inhibition of LSD1 using either RNAi or by the momoamine oxidase inhibitor tranylcypromine (TC) in primary human erythroid progenitor cells induces HbF to therapeutic levels. However, TC treatment has potentially problematic side effects, and at high concentrations decreases adult b-globin mRNAs and impairs erythroid maturation. We have now investigated another LSD1 inhibitor, RN-1, which is a cell-permeable TC analog that acts as a potent, irreversible inhibitor of LSD1 with a lower IC50 than TC. We investigated in vivo effects of RN-1 on γ-globin gene expression and erythroid physiology in a transgenic mouse model of SCD which expresses human α- and sickle β-globin, and has many genetic, hematologic, and pathophysiological features found in SCD patients, including irreversibly sickled RBCs, hemolytic anemia, high reticulocyte counts, hepatosplenomegaly and organ pathology. We found a robust increase in human fetal γ-globin (15-fold) and murine embryonic εY- and βH1-globin mRNAs (36 and 54-fold) and 4-fold increases in human HbF in SCD mice following repeated RN-1 treatment (at 10 μg/g body weight) within 4 weeks. Further, irreversibly sickled RBCs were significantly reduced, and RBC lifespan increased markedly in RN-1-treated SCD mice, leading to significantly decrease pathophysiologic indicators (hemolysis, splenomegaly, and organ necrosis) compared to untreated SCD mice. To begin to evaluate potential effects of RN-1 on erythroid progenitor cells from patients with SCD, peripheral blood from 5 adult SCD patients was cultured with RN-1 (0.07 to 0.25 μM) in a 2-phase progenitor assay, with mRNA analyzed on day 12 and F-reticulocytes on day 13-14 of the erythroid differentiation phase. RN-1 treated progenitors demonstrated a mean 3.4-fold higher g-globin mRNA (p=0.04) and 5% higher absolute F-reticulocytes than were observed in untreated progenitors from the same subject, with responses occurring in 5/5 subjects' assays. These preclinical studies provide additional evidence that modulating LSD-1 activity is a promising approach to inducing HbF expression as a mechanism to reduce clinical severity of SCD. Disclaimer: "Research reported in this publication was supported by the NHLBI under Award Number P50HL118006. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health" R01 DK052962 10A1 R42-HL-110727 Disclosures No relevant conflicts of interest to declare.
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Campbell, Andrew, Osamu Tanabe, Rebekah Urbonya, Andrea Mathias, Lihong Shi, Kwaku Osei Bonsu, Rhonda Douglas, et al. "Analysis of Fetal Hemoglobin Expression within Humanized Sickle Cell Disease Mice Overexpressing the TR2/4 Transgene." Blood 116, no. 21 (November 19, 2010): 1619. http://dx.doi.org/10.1182/blood.v116.21.1619.1619.
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Abstract Abstract 1619 Background: Sickle Cell Disease (SCD) is a chronic debilitating hematologic condition caused by a missense mutation within the adult beta globin gene leading to significant morbidity and mortality. Increased Fetal Hemoglobin production has been shown to significantly ameliorate SCD symptoms and improve survival. A novel specific DNA-binding factor DRED (direct repeat erythroid definitive) was recently identified that regulated epsilon and gamma globin gene expression (Tanimoto et al Genes Dev 2000). Purification of DRED revealed that it harbored the nuclear orphan hormone receptors, TR2/TR4, as its DNA binding core (Tanabe et al EMBO 2002). Overexpression of TR2/TR4 Transgene within Human Beta Globin Yeast Artificial Chromosome Transgenic Mice resulted in 4-fold induction of the gamma globin mRNA levels (Tanabe et al EMBO 2007). Therefore, we wanted to determine if the overexpression of TR2/TR4 within a humanized sickle cell disease model would result in fetal hemoglobin induction. Methods: Humanized Homozygous Knock-In UAB-Sickle Cell (UAB-Hbahα/hα Hbbhβs/hβs) Mice (Wu et al Blood 2006) was mated to TR2/TR4 Overexpressing Mice (TgTR2/TR4) to generate homozygous SS-TR2/TR4 compound heterozygotes (UAB-Hba hα/hα Hbb hβs/hβs TgTR2/TR4). We generated four 2–3 month old homozygous SS-TR2/TR4 transgenic mice and compared hemoglobin F levels, complete blood cell counts and % body weight (liver, spleen, kidney) to six 2–3 month old homozygous SS mice (Hbahα/hα Hbb hβs/hβs)without the overexpressing TgTR2/TR4. Tail PCR genotyping of all sickle cell mice (with and without TgTR2/TR4) and Hemoglobin F(Hgb F) and Sickle (HgbS) levels were confirmed by HPLC Hemoglobin electrophoresis. Results: The mean Hgb F: 7.8% (n=6, sd 1.63+/−) in the homozygous SS control mice vs. 16.5% (n=4, sd 2.64+/−)in the homozygous SS-TR2/4 Mice (2 Fold higher). Hematologic profile revealed a mean Hct: 25.2 (n=6, sd 5.50 +/−) mean MCV: 75.4 (n=6, sd 10+/−) and a mean WBC: 22.6 (n= 6, sd 13.9 +/−) in the homozygous SS control mice vs. a mean Hct: 31.25(n=4, sd 6.89+/−), mean MCV: 61(n=4, sd 3.5+/−) mean WBC: 16.3(n= 4, sd 5.99+/−) in the homozygous SS-TR2/TR4 mice. Lastly, initial organ (spleen, liver, kidney) pathology evaluation revealed decreased % body weight (bw) in homozygous SS TR2/TR4 Mice vs. homozygous SS controls: 1) Spleen %bw: 4.3% vs. 3.5% TgTR2/TR4), 2) Liver % bw: 8.8% vs. 7.7% TgTR2/TR4), and 3) Kidney %bw: 1.14% vs. 1.02% TgTR2/TR4). Conclusions: Our preliminary analysis revealed that TR2/TR4 overexpression within a humanized sickle cell disease mouse model resulted in a 2-fold induction of fetal hemoglobin based on HPLC hemoglobin electrophoresis. Further, increased TR2/TR4 overexpression improved anemia and organomegaly within sickle cell disease mice. TR2/TR4 may be an attractive target for fetal hemoglobin induction for the treatment of sickle cell disease. Ongoing studies will determine if TR2/TR4 decreases organ specific disease pathology. We will also determine the cellular distribution of fetal hemoglobin in future studies. Disclosures: No relevant conflicts of interest to declare.
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Buekers, Jurgen, Madlen David, Gudrun Koppen, Jos Bessems, Martin Scheringer, Erik Lebret, Denis Sarigiannis, et al. "Development of Policy Relevant Human Biomonitoring Indicators for Chemical Exposure in the European Population." International Journal of Environmental Research and Public Health 15, no. 10 (September 21, 2018): 2085. http://dx.doi.org/10.3390/ijerph15102085.
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The European Union’s 7th Environmental Action Programme (EAP) aims to assess and minimize environmental health risks from the use of hazardous chemicals by 2020. From this angle, policy questions like whether an implemented policy to reduce chemical exposure has had an effect over time, whether the health of people in specific regions or subpopulations is at risk, or whether the body burden of chemical substances (the internal exposure) varies with, for example, time, country, sex, age, or socio-economic status, need to be answered. Indicators can help to synthesize complex scientific information into a few key descriptors with the purpose of providing an answer to a non-expert audience. Human biomonitoring (HBM) indicators at the European Union (EU) level are unfortunately lacking. Within the Horizon2020 European Human Biomonitoring project HBM4EU, an approach to develop European HBM indicators was worked out. To learn from and ensure interoperability with other European indicators, 15 experts from the HBM4EU project (German Umweltbundesamt (UBA), Flemish research institute VITO, University of Antwerp, European Environment Agency (EEA)), and the World Health Organization (WHO), European Core Health Indicator initiative (ECHI), Eurostat, Swiss ETH Zurich and the Czech environmental institute CENIA, and contributed to a workshop, held in June 2017 at the EEA in Copenhagen. First, selection criteria were defined to evaluate when and if results of internal chemical exposure measured by HBM, need to be translated into a European HBM-based indicator. Two main aspects are the HBM indicator’s relevance for policy, society, health, and the quality of the biomarker data (availability, comparability, ease of interpretation). Secondly, an approach for the calculation of the indicators was designed. Two types of indicators were proposed: ‘sum indicators of internal exposure’ derived directly from HBM biomarker concentrations and ‘indicators for health risk’, comparing HBM concentrations to HBM health-based guidance values (HBM HBGVs). In the latter case, both the percentage of the studied population exceeding the HBM HBGVs (PE) and the extent of exceedance (EE), calculated as the population’s exposure level divided by the HBM HBGV, can be calculated. These indicators were applied to two examples of hazardous chemicals: bisphenol A (BPA) and per- and polyfluoroalkyl substances (PFASs), which both have high policy and societal relevance and for which high quality published data were available (DEMOCOPHES, Swedish monitoring campaign). European HBM indicators help to summarize internal exposure to chemical substances among the European population and communicate to what degree environmental policies are successful in keeping internal exposures sufficiently low. The main aim of HBM indicators is to allow follow-up of chemical safety in Europe.
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Certal, Catarina, and Milene Medeiros. "IMPACT OF THE HBM PSYCHOTHERAPEUTIC MODEL ON ANXIETY DISORDER: A CASE STUDY." Advances in Social Sciences Research Journal 8, no. 3 (March 11, 2021): 35–44. http://dx.doi.org/10.14738/assrj.83.9811.
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Generalized anxiety disorder (GAD) is characterized by excessive worrying and/or fear in everyday contexts, for at least 6 months (APA, 2014). The study participant is female, 41 years old and she has severe anxiety symptoms. We used as a method a psychodiagnosis with a clinical interview, following the assessment protocol of the Human Behavior Map Model (HBM), the Beck Anxiety Inventory (BAI), the Pittsburgh Sleep Quality Index and the Beck Depression Inventory - Second Edition (BDI-II). The theoretical framework adopted was the HBM Psychotherapeutic Model, in which the intervention was anchored on the human behavior map. This map describes the conscious and unconscious processes of the human mind. HBM has two techniques to release emotional states: athenese and morfese (Certal et al., 2016). This intervention led to the improvement of the studied variables in the participant, particularly the reduction of the GAD symptoms.
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Perry, Jade, Anke J. Roelofs, Claire Mennan, Helen S. McCarthy, Alison Richmond, Susan M. Clark, Anna H. K. Riemen, Karina Wright, Cosimo De Bari, and Sally Roberts. "Human Mesenchymal Stromal Cells Enhance Cartilage Healing in a Murine Joint Surface Injury Model." Cells 10, no. 8 (August 6, 2021): 1999. http://dx.doi.org/10.3390/cells10081999.
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Human umbilical cord (hUC)- or bone marrow (hBM)-derived mesenchymal stromal cells (MSCs) were evaluated as an allogeneic source of cells for cartilage repair. We aimed to determine if they could enhance healing of chondral defects with or without the recruitment of endogenous cells. hMSCs were applied into a focal joint surface injury in knees of adult mice expressing tdTomato fluorescent protein in cells descending from Gdf5-expressing embryonic joint interzone cells. Three experimental groups were used: (i) hUC-MSCs, (ii) hBM-MSCs and (iii) PBS (vehicle) without cells. Cartilage repair was assessed after 8 weeks and tdTomato-expressing cells were detected by immunostaining. Plasma levels of pro-inflammatory mediators and other markers were measured by electrochemiluminescence. Both hUC-MSC (n = 14, p = 0.009) and hBM-MSC (n = 13, p = 0.006) treatment groups had significantly improved cartilage repair compared to controls (n = 18). While hMSCs were not detectable in the repair tissue at 8 weeks post-implantation, increased endogenous Gdf5-lineage cells were detected in repair tissue of hUC-MSC-treated mice. This xenogeneic study indicates that hMSCs enhance intrinsic cartilage repair mechanisms in mice. Hence, hMSCs, particularly the more proliferative hUC-MSCs, could represent an attractive allogeneic cell population for treating patients with chondral defects and perhaps prevent the onset and progression of osteoarthritis.
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Longo, Valentina, Angiola Forleo, Lucia Giampetruzzi, Pietro Siciliano, and Simonetta Capone. "Human Biomonitoring of Environmental and Occupational Exposures by GC-MS and Gas Sensor Systems: A Systematic Review." International Journal of Environmental Research and Public Health 18, no. 19 (September 29, 2021): 10236. http://dx.doi.org/10.3390/ijerph181910236.
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Environmental chemicals and contaminants coming from multiple external sources enter the human body, determining a potential risk for human health. Human biomonitoring (HBM), measuring the concentrations of biomarkers in human specimens, has become an emerging approach for assessing population-wide exposure to hazardous chemicals and health risk through large-scale studies in many countries. However, systematic mapping of HBM studies, including their characteristics, targeted hazardous pollutants, analytical techniques, and sample population (general population and occupationally exposed workers), has not been done so far. We conducted a systematic review of the literature related to airborne hazardous pollutants in biofluids to answer the following questions: Which main chemicals have been included in the literature, which bodily fluids have been used, and what are the main findings? Following PRISMA protocol, we summarized the publications published up to 4 February 2021 of studies based on two methods: gas-chromatography/mass spectrometry (GC/MS) and electronic noses (e-noses). We screened 2606 records and 117 publications were included in the analysis, the most based on GC/MS analysis. The selected HBM studies include measurements of biomarkers in different bodily fluids, such as blood, urine, breast milk, and human semen as well as exhaled air. The papers cover numerous airborne hazardous pollutants that we grouped in chemical classes; a lot of hazardous and noxious compounds, mainly persistent organic pollutants (POPs) and volatile organic compounds (VOCs), have been detected in biological fluids at alarming levels. The scenario that emerged from this survey demonstrates the importance of HBM in human exposure to hazardous pollutants and the need to use it as valid tool in health surveillance. This systematic review represents a starting point for researchers who focus on the world of pollutant biomonitoring in the human body and gives them important insights into how to improve the methods based on GC/MS. Moreover, it makes a first overview of the use of gas sensor array and e-noses in HBM studies.
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Zartaloudi, A. "Health Belief Model (HBM) and vaccination during pandemics." European Psychiatry 65, S1 (June 2022): S308. http://dx.doi.org/10.1192/j.eurpsy.2022.786.
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Introduction With the COVID-19 pandemic recognized as a major threat to human health, promoting vaccination is of paramount importance to public health. Objectives To examine the association between factors of the Health Belief Model (HBM) and intentions to be vaccinated against COVID-19, when a vaccine becomes available. Methods A literature review has been made through PubMed database. Results The HBM dimensions “perceived barriers”, “perceived benefits” and “perceived severity” were considered to be significant predictors of acceptance of vaccinations. The HBM constructs of cues to action (trust in third-party information sources), perceived severity of and susceptibility to COVID-19, and beliefs about the protection benefits of a COVID-19 vaccine, subsequently may elicit willingness to vaccinate. Individual predictors of vaccination were believing the vaccine is effective at preventing COVID-19, recalling their doctor recommending the vaccine. Common perceived barriers against vaccination included believing the vaccine could give people the virus, believing the vaccine can make individuals ill afterwards and preferring to develop immunity “naturally”. Patients who delayed and refused vaccine doses were more likely to have vaccine safety concerns and perceive fewer benefits associated with vaccines. Conclusions HBM is an effective tool for identifying facilitators and barriers to health behaviors. Health promotion should make use of the HBM, as the model provides a theoretically understanding of the dynamics that may enable the success of important health-related policy in the wake of COVID-19 and future pandemics and identifies the communication mechanisms that must be leveraged by governments and authorities in enforcing policy. Disclosure No significant relationships.
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Palomero-Gallagher, Nicola, Brent A. Vogt, Axel Schleicher, Helen S. Mayberg, and Karl Zilles. "Receptor architecture of human cingulate cortex: Evaluation of the four-region neurobiological model." Human Brain Mapping 30, no. 8 (August 2009): 2336–55. http://dx.doi.org/10.1002/hbm.20667.
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Joseph, Joanneia Selin, Julia Wirza Mohd Zawawi, and Akmar Hayati Ahmad Ghazali. "MEDIA AND HEALTH COMMUNICATION OF COVID-19 TOWARDS HEALTH BELIEF MODEL." Special Issue 1, Year 2022 12, S1 (June 17, 2022): 67–76. http://dx.doi.org/10.47836/ajac.12.s1.06.
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The moment when WHO declared the COVID-19 disease as a pandemic, public immediately switch on to access the media for every bit of information regarding the disease. This is because media is the mediator for health communication between the government and the people. By understanding the risk and danger, the media role in creating health awareness could potentially help to improve better health outcomes. They have the capability to influence one’s health behaviours and response to the disease. Health communication is a key factor for saving lives in this pandemic. Thus, this review paper aims to assess the media’s health communication strategies of promoting preventive behaviours to COVID-19, and the associated role of Health Belief Model (HBM) in it. The purpose is to examine (a) the relationship between media and health communication strategies towards COVID-19 preventive behaviours based on HBM and the (b) predictors that engage in preventive behaviours. Utilizing HBM components is crucial for this study as it has been widely applied to study human-related behaviours. This research will allow identifying which predictors of HBM could possibly improve and make the public obey with their preventive behaviours. Moreover, the application of HBM could be a good tool to envision the exact preventive practices among Malaysian population, hence implementing the strategies in their platform for a better health outcome.
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Zakar, Rubeena, Ain ul Momina, Ruhma Shahzad, Sara Shahzad, Mahwish Hayee, Muhammad Zakria Zakar, and Florian Fischer. "COVID-19 Vaccination Acceptance in the Context of the Health Belief Model: Comparative Cross-Sectional Study in Punjab, Pakistan." International Journal of Environmental Research and Public Health 19, no. 19 (October 8, 2022): 12892. http://dx.doi.org/10.3390/ijerph191912892.
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One of the models that could be used to understand the adoption of vaccine uptake is the Health Belief Model (HBM). The aim of this study is to assess the role of HBM constructs and Perceived Health Status (PHS) on the vaccination status of individuals and to understand the role of socio-demographic variables on HBM scoring. A comparative cross-sectional telephone survey was conducted among 1325 vaccinated (60.0%) and non-vaccinated (40.0%) individuals aged 40 years and above in July 2021 in Punjab province, Pakistan. A higher level of education was the strongest predictor of positive HBM. All constructs of HBM, PHS and cues-to-action were significant predictors of COVID-19 vaccination uptake, with perceived benefits as the strongest predictor. In order to expand the vaccination coverage, double-pronged interventions utilizing both information and communication technology and human resources should be designed that address each barrier perceived by individuals and understandably communicate the benefits of COVID-19 vaccination to the broader population.
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Colles, Ann, Dries Coertjens, Bert Morrens, Elly Den Hond, Melissa Paulussen, Liesbeth Bruckers, Eva Govarts, et al. "Human Biomonitoring Data Enables Evidence-Informed Policy to Reduce Internal Exposure to Persistent Organic Compounds: A Case Study." International Journal of Environmental Research and Public Health 18, no. 11 (May 22, 2021): 5559. http://dx.doi.org/10.3390/ijerph18115559.
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Human biomonitoring (HBM) monitors levels of environmental pollutants in human samples, which often is a topic of concern for residents near industrially contaminated sites (ICSs). Around an ICS area in Menen (Belgium), including a (former) municipal waste incinerator and a metal recovery plant, increasing environmental concentrations of dioxins and polychlorinated biphenyls (PCBs) were observed, causing growing concern among residents and authorities. The local community succeeded in convincing the responsible authorities to investigate the problem and offer research funding. Persistent organic pollutants (POPs) were measured in two consecutive HBM studies (2002–2006 and 2010–2011), in the context of the Flemish Environment and Health Study (FLEHS), as well as in soil and locally produced food. Meanwhile, local authorities discouraged consumption of locally produced food in a delineated area of higher exposure risk. Ultimately, HBM and environmental data enabled tailored dietary recommendations. This article demonstrates the usefulness of HBM in documenting the body burdens of residents near the ICS, identifying exposure routes, evaluating remediating actions and providing information for tailored policy strategies aiding to further exposure reduction. It also highlights the role of the local stakeholders as an example of community-based participatory research and how such an approach can create societal support for research and policy.
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Lawrence, Logan, Andrew Cottrill, Amrita Valluri, Gaetano Marenzi, Krista Denning, Jagan Valluri, Pier Claudio, and James Day. "Minimally Manipulative Method for the Expansion of Human Bone Marrow Mesenchymal Stem Cells to Treat Osseous Defects." International Journal of Molecular Sciences 20, no. 3 (January 31, 2019): 612. http://dx.doi.org/10.3390/ijms20030612.
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Lack of standardization of clinically compliant culture protocols of mesenchymal stem cells for re-implantation in humans have hindered clinical progress in the field of tissue regeneration to repair maxillofacial and orthopedic defects. The goal of this study was to establish a clinically relevant osteogenic protocol for collection and expansion of autologous stem cells to be used at Marshall University for re-implantation and repair of maxillofacial and orthopedic conditions. Human bone marrow (hBM) samples were collected from patients undergoing intramedullary nail fixation for closed femoral fractures. hBM mesenchymal cells were expanded by growing them first in Petri dishes for two weeks, followed by a week of culture using Perfecta 3D Hanging Drop Plates®. Various scaffold materials were tested and analyzed for cellular integration, vitality, and differentiation capacity of harvested hBM-MSCs including: 60/40 blend of hydroxyapatite biomatrix; Acellular bone composite discs; Allowash®, cancellous bone cubes; PLGA (poly lactic-co-glycolic acid); and Woven chitin derived fiber. We found that the 3D spheroid culture allowed production of hBM mesenchymal cells that retained osteoblast differentiation capacity over a monolayer culture of hBM-MSCs without the need to use chemical or hormonal modulation. We also observed that hydroxyapatite and Allowash cancellous bone scaffolds allowed better cell integration and viability properties as compared to other materials tested in this study. In conclusion, the multimodal culture methodology we developed creates actively differentiating stem-cell spheroids that can then be readily utilized in clinical practices to improve the regeneration of tissues of the head and the body.
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Feng, Jiayu, Weifeng Yao, Yihan Zhang, Andy Peng Xiang, Dongdong Yuan, and Ziqing Hei. "Intravenous Anesthetics Enhance the Ability of Human Bone Marrow-Derived Mesenchymal Stem Cells to Alleviate Hepatic Ischemia-Reperfusion Injury in a Receptor-Dependent Manner." Cellular Physiology and Biochemistry 47, no. 2 (2018): 556–66. http://dx.doi.org/10.1159/000489989.
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Background/Aims: The degree of hepatic ischemia-reperfusion injury (HIRI) is highly relevant to the incidence of postoperative liver failure and mortality. Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been shown to migrate to the liver and restore the damaged liver. Intravenous anesthetics are commonly used in the perioperative period; however, it is not yet known whether they have an influence on the functions of BM-MSCs and eventually affect the recovery of HIRI. Methods: A rat model of HIRI and a hypoxia-reoxygenation (H/R) model using L02 cells were generated, and human BM-MSCs (hBM-MSCs) were injected through the portal vein or co-cultured with L02 cells in a Transwell system, respectively. Three intravenous anesthetics, namely, dexmedetomidine, midazolam, and propofol, were given as pretreatments to hBM-MSCs. Quantitative real-time PCR for growth factors (HGF, FGF, VEGF, and IGF) and a migration assay were used to detect the paracrine and migration abilities of hBM-MSCs. NF-κB expression was detected using an immunofluorescence method. Furthermore, three receptor inhibitors, namely, yohimbine, PK11195, and bicuculline, were given to explore whether the three anesthetics worked in a receptor-dependent manner. Results: Preconditioning with dexmedetomidine and midazolam, but not propofol, enhanced the efficacy of hBM-MSCs in HIRI. Dexmedetomidine and midazolam, but not propofol, changed the paracrine spectrum and NF-κB p65 nuclear translocation of hBM-MSCs co-cultured with L02 cells after H/R injury. All three anesthetics enhanced the migration ability of hBM-MSCs when cultured in L02 H/R conditioned medium. However, the addition of receptor antagonists resulted in an opposite tendency. Conclusions: The intravenous anesthetics dexmedetomidine and midazolam enhanced the liver protective effects of hBM-MSCs during HIRI more effectively than propofol, by binding with their receptors and regulating the paracrine effect, migration ability, and NF-κB p65 nuclear translocation of hBM-MSCs.
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Khumros, Waraporn, Arnond Vorayingyong, Siriluck Suppapitiporn, Thanapoom Rattananupong, and Vitool Lohsoonthorn. "Effectiveness of modified health belief model-based intervention to reduce body mass index for age in overweight junior high school students in Thailand." Journal of Health Research 33, no. 2 (March 11, 2019): 162–72. http://dx.doi.org/10.1108/jhr-08-2018-0065.
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PurposeThe purpose of this paper is to determine the effectiveness of a modified HBM-based intervention to reduce body mass index (BMI) for age in overweight junior high school students.Design/methodology/approachA cluster-randomized controlled trial was conducted in the first and second years of a junior high school in the center of Thailand. In total, 24 classrooms were randomly assigned to a modified health belief model intervention arm (HBMIA), and 24 classrooms were randomly assigned to a traditional school health education arm (control). In total, 479 students who were overweight (BMI forage = median +1 SD, aged 12–15 years) participated in the study. The HBMIA used the health belief model (HBM) as a motivator for behavioral strategies that included modifying diet and participating in physical activity. BMI, health knowledge and behavior for preventing obesity were recorded at baseline and at six months. A multilevel regression model was performed to calculate mean difference between HBMIA and control group.FindingsThe students who participated in the HBMIA showed a decrease in BMI of 1.76 kg/m2, while those who participated in the control showed an increase in BMI of 1.13 kg/m2, with a mean difference of –2.88 kg/m2(95% CI =–3.01 to –2.75), an improvement in health knowledge (mean difference 27.28; 95% CI =26.15–28.41) and an improvement in health behavior (mean difference 23.54; 95% CI =22.60–24.48).Originality/valueA modified HBM-based intervention to reduce BMI for age is effective in overweight junior high school students.
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Bentivegna, Angela, Gaia Roversi, Gabriele Riva, Laura Paoletta, Serena Redaelli, Mariarosaria Miloso, Giovanni Tredici, and Leda Dalprà. "The Effect of Culture on Human Bone Marrow Mesenchymal Stem Cells: Focus on DNA Methylation Profiles." Stem Cells International 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/5656701.
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Human bone marrow mesenchymal stem cells (hBM-MSCs) are the best characterized multipotent adult stem cells. Their self-renewal capacity, multilineage differentiation potential, and immunomodulatory properties have indicated that they can be used in many clinical therapies. In a previous work we studied the DNA methylation levels of hBM-MSC genomic DNA in order to delineate a kind of methylation signature specific for early and late passages of culture. In the present work we focused on the modification of the methylation profiles of the X chromosome and imprinted loci, as sites expected to be more stable than whole genome. We propose a model where cultured hBM-MSCs undergo random modifications at the methylation level of most CGIs, nevertheless reflecting the original methylation status. We also pointed out global genome-wide demethylation connected to the long-term culture and senescence. Modification at CGIs promoters of specific genes could be related to the decrease in adipogenic differentiation potential. In conclusion, we showed important changes in CGIs methylation due to long-termin vitroculture that may affect the differentiation potential of hBM-MSCs. Therefore it is necessary to optimize the experimental conditions forin vitroexpansion in order to minimize these epigenetic changes and to standardize safer procedures.
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Argentati, Chiara, Francesco Morena, Chiara Fontana, Ilaria Tortorella, Carla Emiliani, Loredana Latterini, Giulia Zampini, and Sabata Martino. "Functionalized Silica Star-Shaped Nanoparticles and Human Mesenchymal Stem Cells: An In Vitro Model." Nanomaterials 11, no. 3 (March 18, 2021): 779. http://dx.doi.org/10.3390/nano11030779.
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The biomedical translational applications of functionalized nanoparticles require comprehensive studies on their effect on human stem cells. Here, we have tested neat star-shaped mesoporous silica nanoparticles (s-MSN) and their chemically functionalized derivates; we examined nanoparticles (NPs) with similar dimensions but different surface chemistry, due to the amino groups grafted on silica nanoparticles (s-MSN-NH2), and gold nanoseeds chemically adsorbed on silica nanoparticles (s-MSN-Au). The different samples were dropped on glass coverslips to obtain a homogeneous deposition differing only for NPs’ chemical functionalization and suitable for long-term culture of human Bone Marrow–Mesenchymal stem cells (hBM-MSCs) and Adipose stem cells (hASCs). Our model allowed us to demonstrate that hBM-MSCs and hASCs have comparable growth curves, viability, and canonical Vinculin Focal adhesion spots on functionalized s-MSN-NH2 and s-MSN-Au as on neat s-MSN and control systems, but also to show morphological changes on all NP types compared to the control counterparts. The new shape was stem-cell-specific and was maintained on all types of NPs. Compared to the other NPs, s-MSN-Au exerted a small genotoxic effect on both stem cell types, which, however, did not affect the stem cell behavior, likely due to a peculiar stem cell metabolic restoration response.
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Zandi, Sasan, John E. Dick, Faiyaz Notta, and Naoya Takayama. "Distinct Regulatory Networks Govern Human Hematopoietic Stem Cell Across Development." Blood 126, no. 23 (December 3, 2015): 2375. http://dx.doi.org/10.1182/blood.v126.23.2375.2375.
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Abstract Introduction: Much of our fundamental understanding of stem cell biology comes from studies of hematopoiesis where single cells produce differentiated progeny while still retaining the ability to produce daughter stem cells (self-renewal). The cardinal property of a stem cell, whether normal or malignant, is self-renewal; the key biological process that ensures the ability of the stem cell to maintain long-term clonal growth. However, our understanding of the molecular basis of self-renewal in human hematopoiesis is limited. At the embryonic stage fetal liver is the main source of hematopoiesis; from week 6 of gestation until before birth. At this stage HSCs are in a different microenvironment but capable of self-renewing and differentiation to the full spectrum of blood lineages. While murine studies uncovered several intrinsic differences between fetal and adult HSCs, a comprehensive analysis of human HSC compartment across development is lacking. In this study we have combined HSC purification methods and xenograft quantitative assay in conjunction with low input RNA sequencing and Enhanced Reduced Representation Bisulfite Sequencing (ERRBS) to provide a comprehensive functional and molecular outlook of human stem cell compartment across development. Results: We followed the dynamics of four sub-fractions of CD34+CD38- divided by CD90 and CD49f expression across human blood development: fetal liver (hFL) and adult bone marrow (hBM). Using xenograft model, we identified human long, intermediate and short term HSCs in hFL and hBM. 5 single CD90+CD49f+ hFL cells were capable of sustaining the multilineage graft for over 52 weeks up to tertiary recipient, while BM cells only last for 20 weeks in the primary recipient. The frequency of LT-HSC in the CD90+CD49f+ compartment goes from 1/8 in hFL to 1/50 in hBM. hFL CD90-CD49f+ cells showed an intermediate repopulation capacity up to 44 weeks in secondary recipient. On average 10% of hFL long term HSC (LT-HSC) were in S/G2/M phase, in contrast only 0.4% of BM LT-HSC were in S/G2/M phase indicating that hFL HSCs are 20 times more in cycle compare to BM. We found that 320 genes were expressed differentially between LT-HSC and multipotent progenitors (MPP) in hBM as oppose to only 32 genes found to be differentially expressed in hFL (FDR<0.1). Interestingly, we found only 2 genes in common between these two groups. ERRBS showed an overall increase in methylation of HSC compartment in hBM compare to hFL and gradual demethylation of lineage associated genes in MPP. Conclusion: Our data indicate that there are distinct regulatory networks that govern hFL and hBM HSC self-renewal. We found very little differences in gene expression between all hFL HCS compartments (average 20 genes) compare to hBM (average 224), indicating that by adulthood self-renewal is becoming more restricted to the LT-HSC compartment. Disclosures No relevant conflicts of interest to declare.
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Naranjo-Hernández, David, Amparo Callejón-Leblic, Željka Lučev Vasić, MirHojjat Seyedi, and Yue-Ming Gao. "Past Results, Present Trends, and Future Challenges in Intrabody Communication." Wireless Communications and Mobile Computing 2018 (March 11, 2018): 1–39. http://dx.doi.org/10.1155/2018/9026847.
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Intrabody communication (IBC) is a wireless communication technology using the human body to develop body area networks (BANs) for remote and ubiquitous monitoring. IBC uses living tissues as a transmission medium, achieving power-saving and miniaturized transceivers, making communications more robust against external interference and attacks on the privacy of transmitted data. Due to these advantages, IBC has been included as a third physical layer in the IEEE 802.15.6 standard for wireless body area networks (WBANs) designated as Human Body Communication (HBC). Further research is needed to compare both methods depending on the characteristics of IBC application. Challenges remain for an optimal deployment of IBC technology, such as the effect of long-term use in the human body, communication optimization through more realistic models, the influence of both anthropometric characteristics and the subject’s movement on the transmission performance, standardization of communications, and development of small-size and energy-efficient prototypes with increased data rate. The purpose of this work is to provide an in-depth overview of recent advances and future challenges in human body/intrabody communication for wireless communications and mobile computing.
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Prabhakar, A., Ameet Kurthukoti, and Pranjali Gupta. "Cariogenicity and Acidogenicity of Human Milk, Plain and Sweetened Bovine Milk: An In Vitro Study." Journal of Clinical Pediatric Dentistry 34, no. 3 (April 1, 2010): 239–47. http://dx.doi.org/10.17796/jcpd.34.3.lk08l57045043444.
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The objective of the present study was to determine the acidogenicity and cariogenicity of human breast milk and plain and sweetened packaged bovine milk. Study Design: First all milk specimens were inoculated with a cariogenic strain of Streptococcus mutans(SM). The culture pH and number of colony forming units (cfus) was assessed. Second, the buffer capacity of all milk specimens was evaluated by mixing with acid. Finally, enamel windows were created on extracted primary maxillary incisors and colonized with SM. Enamel demineralization and caries progression were assessed visually, histologically, and radiographically at the end of twelve weeks. Results: Plain and sweetened packaged bovine milk (BM) supported greater bacterial growth and caused more fermentation than human breast milk (HBM). The buffer capacity values for plain and sweetened bovine milk were highest;HBM, however, had poor buffering capacity. The progression of the carious lesions into the dentin was most severe for the sweetened bovine milk. Conclusions: HBM and plain bovine milk are relatively cariogenic in an in vitro caries model in the absence of saliva. However, supplementation with sugar exponentially enhances the cariogenic potential of the natural milk.