Search results for: vibration therapy

Authors: Mirco Tarozzi, Giacomo Pignagnoli, Andrea Benedetti

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Structural systems are often subjected to degradation processes due to different kind of phenomena like unexpected loadings, ageing of the materials and fatigue cycles. This is true especially for bridges, in which their safety evaluation is crucial for the purpose of a design of planning maintenance. This paper discusses the experimental evaluation of the stiffness reduction from frequency changes due to uniform damage scenario. For this purpose, a 1:4 scaled bridge has been built in the laboratory of the University of Bologna. It is made of concrete and its cross section is composed by a slab linked to four beams. This concrete deck is 6 m long and 3 m wide, and its natural frequencies have been identified dynamically by exciting it with an impact hammer, a dropping weight, or by walking on it randomly. After that, a set of loading cycles has been applied to this bridge in order to produce a uniformly distributed crack pattern. During the loading phase, either cracking moment and yielding moment has been reached. In order to define the relationship between frequency variation and loss in stiffness, the identification of the natural frequencies of the bridge has been performed, before and after the occurrence of the damage, corresponding to each load step. The behavior of breathing cracks and its effect on the natural frequencies has been taken into account in the analytical calculations. By using a sort of exponential function given from the study of lot of experimental tests in the literature, it has been possible to predict the stiffness reduction through the frequency variation measurements. During the load test also crack opening and middle span vertical displacement has been monitored.

Keywords: concrete bridge, damage detection, dynamic test, frequency shifts, operational modal analysis

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Authors: Vinesh Janarthanan, Mohammad H. Rahman

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There are numerous neurological conditions that may result in a loss of motor function. Such conditions may include cerebral palsy, Parkinson’s disease, stroke or multiple sclerosis. Due to impaired motor function, specifically in the hand and arm, living independently becomes tremendously more difficult. Rehabilitation programs are the main method to treat these kinds of disabled individuals. However, these programs require longtime commitment from the clinicians/therapists, demand person to person caring, and typically the treatment duration is usually very long. Aside from the treatment received from the therapist, the continuation of neuroplasticity at home is essential to maximizing development and restoring the biological function. To contribute in this area, we have researched and developed a portable and comfortable hand glove for fine motor skills rehabilitation. The glove provides interactive home-based therapy to engage the patient with simple games. The key to this treatment is the repetition of moving the hand and being capable of positioning the hand in various ways.

Keywords: home based, wearable sensors, glove, rehabilitation, motor function, video games

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Authors: Kira Merigan

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BACKGROUND- Fertility preservation (FP) measures are increasingly recognised as an important consideration for children and adolescents planned to undergo potentially damaging gonadotoxic therapy. Worldwide, there are very few documented cases of FP in young females by way of ovarian stimulation and oocyte cryopreservation.AIM – To report a case series of mature oocyte cryopreservation in 5post-pubertal adolescents aged 14-17 years old, with varied medical conditions requiring gonadotoxic treatment. SETTING-These cases took place via a multidisciplinary team approach at The Royal Children’s Hospital, a large tertiary centre in Melbourne, Australia. INTERVENTION– Ovarian stimulation and oocyte collection was performed as detailed in each case. RESULTS –Across the 5 patients, 3-28 oocytes were retrieved. We report pre-treatment workup, complications, and delays to treatment. CONCLUSION- Oocyte cryopreservation may be a safe alternative to ovarian tissue cryopreservation (OTC) in the adolescent population

Keywords: fertility preservation, adolescent, ovarian stimulation, oocyte cryopreservation

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Authors: E. Mosiniewicz-Szablewska, P. Suchocki, P. C. Morais

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Despite the significant progress in cancer treatment, there is a need to search for new therapeutic methods in order to minimize side effects. Chemotherapy, the main current method of treating cancer, is non-selective and has a number of limitations. Toxicity to healthy cells is undoubtedly the biggest problem limiting the use of many anticancer drugs. The problem of how to kill cancer without harming a patient can be solved by using organic selenium (IV) compounds. Organic selenium (IV) compounds are a new class of materials showing a strong anticancer activity. They are first organic compounds containing selenium at the +4 oxidation level and therefore they eliminate the multidrug-resistance for all tumor cell lines tested so far. These materials are capable of selectively killing cancer cells without damaging the healthy ones. They are obtained by the incorporation of selenous acid (H2SeO3) into molecules of fatty acids of sunflower oil and therefore, they are inexpensive to manufacture. Attaching these compounds to magnetic carriers enables their precise delivery directly to the tumor area and the simultaneous application of the magnetic hyperthermia, thus creating a huge opportunity to effectively get rid of the tumor without any side effects. Polylactic-co-glicolic acid (PLGA) nanocapsules loaded with maghemite (-Fe2O3) nanoparticles and organic selenium (IV) compounds are successfully prepared by nanoprecipitation method. In vitro antitumor activity of the nanocapsules were evidenced using murine melanoma (B16-F10), oral squamos carcinoma (OSCC) and murine (4T1) and human (MCF-7) breast lines. Further exposure of these cells to an alternating magnetic field increased the antitumor effect of nanocapsules. Moreover, the nanocapsules presented antitumor effect while not affecting normal cells. Magnetic properties of the nanocapsules were investigated by means of dc magnetization, ac susceptibility and electron spin resonance (ESR) measurements. The nanocapsules presented a typical superparamagnetic behavior around room temperature manifested itself by the split between zero field-cooled/field-cooled (ZFC/FC) magnetization curves and the absence of hysteresis on the field-dependent magnetization curve above the blocking temperature. Moreover, the blocking temperature decreased with increasing applied magnetic field. The superparamagnetic character of the nanocapsules was also confirmed by the occurrence of a maximum in temperature dependences of both real ′(T) and imaginary ′′ (T) components of the ac magnetic susceptibility, which shifted towards higher temperatures with increasing frequency. Additionally, upon decreasing the temperature the ESR signal shifted to lower fields and gradually broadened following closely the predictions for the ESR of superparamagnetoc nanoparticles. The observed superparamagnetic properties of nanocapsules enable their simple manipulation by means of magnetic field gradient, after introduction into the blood stream, which is a necessary condition for their use as magnetic drug carriers. The observed anticancer and superparamgnetic properties show that the magnetic nanocapsules loaded with organic selenium (IV) compounds should be considered as an effective material system for magnetic drug delivery and magnetohyperthermia inductor in antitumor therapy.

Keywords: cancer treatment, magnetic drug delivery system, nanomaterials, nanotechnology

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Authors: David Robert Irvine

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In the dental restoration sector, there has been a shift to using zirconia. With the ever increasing need to decrease lead times to deliver restorations faster the zirconia is machined in its pre-sintered state instead of grinding the very hard sintered state. As with all machining, there is tool wear and while investigating the tooling used to machine pre-sintered zirconia it became apparent that the wear rate is based more on material build up and abrasion than it is on plastic deformation like conventional metal machining. It also came to light that the tool material can currently not be selected based on wear resistance, as there is no data. Different works have analysed the effect of the individual wear mechanism separately using similar if not the same material. In this work, the testing method used to analyse the wear was a modified from ISO 8688:1989 to use the pre-sintered zirconia and the cutting conditions used in dental to machine it. This understanding was developed through a series of tests based in machining operations, to give the best representation of the multiple wear factors that can occur in machining of pre-sintered zirconia such as 3 body abrasion, material build up, surface welding, plastic deformation, tool vibration and thermal cracking. From the testing, it found that carbide grades with low trans-granular rupture toughness would fail due to abrasion while those with high trans-granular rupture toughness failed due to edge chipping from build up or thermal properties. The results gained can assist the development of these tools and the restorative dental process. This work was completed with the aim of assisting in the selection of tool material for future tools along with a deeper understanding of the properties that assist in abrasive wear resistance and material build up.

Keywords: abrasive wear, cemented carbide, pre-sintered zirconia, tool wear

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Authors: Saule Balmagambetova, Zhenisgul Tlegenova, Saule Madinova

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Cardiotoxicity associated with anticancer treatment, now defined as cancer therapy-related cardiac dysfunction (CTRCD), accompanies cancer patients and negatively impacts their survivorship. Currently, a cardio-oncological service is being created in Kazakhstan based on the provisions of the European Society of Cardio-oncology (ESC) Guidelines. In the frames of a pilot project, a cohort study on CTRCD conditions was initiated at the Aktobe Cancer center. One hundred twenty-eight newly diagnosed breast cancer patients started on doxorubicin and/or trastuzumab were recruited. Echocardiography with global longitudinal strain (GLS) assessment, biomarkers panel (cardiac troponin (cTnI), brain natriuretic peptide (BNP), myeloperoxidase (MPO), galectin-3 (Gal-3), D-dimers, C-reactive protein (CRP)), and other tests were performed at baseline and every three months. Patients were stratified by the cardiovascular risks according to the ESC recommendations and allocated into the risk groups during the pre-treatment visit. Of them, 10 (7.8%) patients were assigned to the high-risk group, 48 (37.5%) to the medium-risk group, and 70 (54.7%) to the low-risk group, respectively. High-risk patients have been receiving their cardioprotective treatment from the outset. Patients were also divided by treatment - in the anthracycline-based 83 (64.8%), in trastuzumab- only 13 (10.2%), and in the mixed anthracycline/trastuzumab group 32 individuals (25%), respectively. Mild symptomatic CTRCD was revealed and treated in 2 (1.6%) participants, and a mild asymptomatic variant in 26 (20.5%). Mild asymptomatic conditions are defined as left ventricular ejection fraction (LVEF) ≥50% and further relative reduction in GLS by >15% from baseline and/or a further rise in cardiac biomarkers. The listed biomarkers were assessed longitudinally in repeated-measures linear regression models during 12 months of observation. The associations between changes in biomarkers and CTRCD and between changes in biomarkers and LVEF were evaluated. Analysis by risk groups revealed statistically significant differences in baseline LVEF scores (p 0.001), BNP (p 0.0075), and Gal-3 (p 0.0073). Treatment groups found no statistically significant differences at baseline. After 12 months of follow-up, only LVEF values showed a statistically significant difference by risk groups (p 0.0011). When assessing the temporal changes in the studied parameters for all treatment groups, there were statistically significant changes from visit to visit for LVEF (p 0.003); GLS (p 0.0001); BNP (p<0.00001); MPO (p<0.0001); and Gal-3 (p<0.0001). No moderate or strong correlations were found between the biomarkers values and LVEF, between biomarkers and GLS. Between the biomarkers themselves, a moderate, close to strong correlation was established between cTnI and D-dimer (r 0.65, p<0.05). The dose-dependent effect of anthracyclines has been confirmed: the summary dose has a moderate negative impact on GLS values: -r 0.31 for all treatment groups (p<0.05). The present study found myeloperoxidase as a promising biomarker of cardiac dysfunction in the mixed anthracycline/trastuzumab treatment group. The hazard of CTRCD increased by 24% (HR 1.21; 95% CI 1.01;1.73) per doubling in baseline MPO value (p 0.041). Increases in BNP were also associated with CTRCD (HR per doubling, 1.22; 95% CI 1.12;1.69). No cases of chemotherapy discontinuation due to cardiotoxic complications have been recorded. Further observations are needed to gain insight into the ability of biomarkers to predict CTRCD onset.

Keywords: breast cancer, chemotherapy, cardiotoxicity, Kazakhstan

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Authors: Paula Pascoal-Faria, Rúben Pereira, Elodie Pinto, Miguel Belbut, Ana Rosa, Inês Sousa, Nuno Alves

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Apple bruise damage from harvesting, handling, transporting and sorting is considered to be the major source of reduced fruit quality, resulting in loss of profits for the entire fruit industry. The three factors which can physically cause fruit bruising are vibration, compression load and impact, the latter being the most common source of bruise damage. Therefore, prediction of the level of damage, stress distribution and deformation of the fruits under external force has become a very important challenge. In this study, experimental and numerical methods were used to better understand the impact caused when an apple is dropped from different heights onto a plastic surface and a conveyor belt. Results showed that the extent of fruit damage is significantly higher for plastic surface, being dependent on the height. In order to support the development of a biomimetic electronic device for the determination of fruit damage, the mechanical properties of the apple fruit were determined using mechanical tests. Preliminary results showed different values for the Young’s modulus according to the zone of the apple tested. Along with the mechanical characterization of the apple fruit, the development of the first two prototypes is discussed and the integration of the results obtained to construct the final element model of the apple is presented. This work will help to reduce significantly the bruise damage of fruits or vegetables during the entire processing which will allow the introduction of exportation destines and consequently an increase in the economic profits in this sector.

Keywords: apple, fruit damage, impact during crop and post-crop, mechanical characterization of the apple, numerical evaluation of fruit damage, electronic device

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Authors: Aref Lashin

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Saudi Arabia vision of 2030 calls for the diversification of energy sources in the Kingdom. Accordingly, Saudi Arabia has launched a promising plan aims to gradually power the major industrial activities in country by renewable and low carbon energy sources. The geothermal sources are among the promising renewable sources that can support the achievement of the country vision and energy mix plan. Saudi Arabia is enriched with several geothermal resources especially in the western and southwestern regions along the Red Sea region. This paper will give an overview on the different geothermal resources (Hydrothermal, Harrats volcanic eruptions and hot dry rocks) of Saudi Arabia, their categories and classifications as well as the different exploration (Geophysical, geological, geochemical, etc) and drilling enhanced during the last few decades. The economic viability and the possible contribution of geothermal resources in the future of renewable energy of Saudi Arabia is discussed. Some case studies from Jizan, Al-Lith, Harrats and Midyan areas are demonstrated. Scenarios of different low and high geothermal applications for possible power generations, as well as other low-grade utilizations, e.g. direct use, district heating & cooling, medical therapy, etc., are presented.

Keywords: KSA vison 2023, energy mix, geothermal resources, applications, Saudi Arabia

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Authors: Alireza Moghtaderi, Negin Khakpour

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Disc Herniation is a common complication in the society and it is one of the main reasons for referring to physical medicine and rehabilitation clinics. Despite of various methods proposed for treatingthis disease, still there is disagreement on success of these methods especially in non-surgical methods, and thus current study aims at determining effect of laser beam and magnet on treatment of Intervertebral Disc Herniation. During a clinical trial study, 80 patients with Intervertebral Disc Herniation underwent a combined package of treatment including magnet, laser beam, PRP and Prolotherapy during 6 months. Average age of patients was 51.25 ± 10.7 with range of 25 – 71 years. 30 men (37.5%) and 50 women (62.5%) took part in the study. average weight of patients was 64.3 ± 7.2 with range of 49 – 79 kg. highest level of Disc Herniation was L5 – S1 with frequency of 17 cases (21.3%). Disc Herniation was severe in 30 cases before treatment, but it reduced to 3 casesafter treatment. This study indicates effect of combined treatment using non-invasive laser beam and magnet therapy on disco genic diseases and mechanical pains of spine is highly effective.

Keywords: hallux, valgus, botulinum toxin a, pain

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Authors: Pampita Chakraborty, Sukumar Mukherjee

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This study was done to determine the bacteriological profile and antibiotic resistance of the isolates and to find out the potential risk factors for infection with multidrug-resistant organisms. Diabetic foot ulcer is a major medical, social, economic problem and a leading cause of morbidity and mortality, especially in the developing countries like India. 25 percent of all diabetic patients develop a foot ulcer at some point in their lives which is highly susceptible to infections and that spreads rapidly, leading to overwhelming tissue destruction and subsequent amputation. Infection with multidrug resistant organisms (MDRO) may increase the cost of management and may cause additional morbidity and mortality. Proper management of these infections requires appropriate antibiotic selection based on culture and antimicrobial susceptibility testing. Early diagnosis of microbial infections is aimed to institute the appropriate antibacterial therapy initiative to avoid further complications. A total of 200 Type 2 Diabetic Mellitus patients with infection were admitted at GD Hospital and Diabetes Institute, Kolkata. 60 of them who developed ulcer during the year 2013 were included in this study. A detailed clinical history and physical examination were carried out for every subject. Specimens for microbiological studies were obtained from ulcer region. Gram-negative bacilli were tested for extended spectrum Beta-lactamase (ESBL) production by double disc diffusion method. Staphylococcal isolates were tested for susceptibility to oxacillin by screen agar method and disc diffusion. Potential risk factors for MDRO-positive samples were explored. Gram-negative aerobes were most frequently isolated, followed by gram-positive aerobes. Males were predominant in the study and majority of the patients were in the age group of 41-60 years. The presence of neuropathy was observed in 80% cases followed by peripheral vascular disease (73%). Proteus spp. (22) was the most common pathogen isolated, followed by E.coli (17). Staphylococcus aureus was predominant amongst the gram-positive isolates. S.aureus showed a high rate of resistance to antibiotic tested (63.6%). Other gram-positive isolates were found to be highly resistant to erythromycin, tetracycline and ciprofloxacin, 40% each. All isolates were found to be sensitive to Vancomycin and Linezolid. ESBL production was noted in Proteus spp and E.coli. Approximately 70 % of the patients were positive for MDRO. MDRO-infected patients had poor glycemic control (HbA1c 11± 2). Infection with MDROs is common in diabetic foot ulcers and is associated with risk factors like inadequate glycemic control, the presence of neuropathy, osteomyelitis, ulcer size and increased the requirement for surgical treatment. There is a need for continuous surveillance of resistant bacteria to provide the basis for empirical therapy and reduce the risk of complications.

Keywords: diabetic foot ulcer, bacterial infection, multidrug-resistant organism, extended spectrum beta-lactamase

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Authors: Tanveer Beg, Yasir H. Siddique, Gulshan Ara, Asfar S. Azmi, Mohammad Afzal

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Doxorubicin is a well-known DNA intercalating chemotherapy drug that is widely used for treatment of different cancers. Its clinical utility is limited due to the observed genotoxic side effects on healthy cells suggesting that newer combination and genoprotective regimens are urgently needed for the management of doxorubicin chemotherapy. Some dietary phytochemicals are well known for their protective mechanism of action and genistein from soy is recognized as an anti-oxidant with similar properties. Therefore, the present study investigates the effect of genistein against the genotoxic doses of doxorubicin by assessing chromosomal aberrations, sister chromatid exchanges, cell cycle kinetics, cell viability, apoptosis, and DNA damage markers in cultured human lymphocytes. Our results reveal that genistein treatment significantly suppresses genotoxic damage induced by doxorubicin. It is concluded that genistein has the potential to reduce the genotoxicity induced by anti-cancer drugs, thereby reducing the chances of developing secondary tumors during the therapy.

Keywords: apoptosis, DNA damage markers, doxorubicin, genistein, genotoxicity, human lymphocyte culture

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Authors: S. Zolghadri, M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani

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In this study, the absorbed dose of human organs after injection of ¹⁷⁷Lu-DOTATOC was studied based on the biodistribution of the complex in adenocarcinoma breast cancer bearing mice. For this purpose, the biodistribution of the radiolabelled complex was studied and compartmental modeling was applied to calculate the absorbed dose with high precision. As expected, ¹⁷⁷Lu-DOTATOC illustrated a notable specific uptake in tumor and pancreas, organs with high level of somatostatin receptor on their surface and the effectiveness of the radio-conjugate for targeting of the breast adenocarcinoma tumors was indicated. The elicited results of modeling were the exponential equations, and those are utilized for obtaining the cumulated activity data by taking their integral. The results also exemplified that non-target absorbed-doses such as the liver, spleen and pancreas were approximately 0.008, 0.004, and 0.039, respectively. While these values were so much lower than target (tumor) absorbed-dose, it seems due to this low toxicity, this complex is a good agent for therapy.

Keywords: ¹⁷⁷Lu, breast cancer, compartmental modeling, dosimetry

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Authors: Benedikt Munzar, Jagraj Singh, Alice Mei, David Musheyev, Sandeep Gandhi

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Clostridium is a gram-positive, anaerobic, spore-forming rod that is not commonly identified as a primary human pathogen. Here is presented a case of a 60-year-old patient with a history of opioid use disorder who underwent a number of abdominal surgeries for small bowel obstruction. His hospital course was complicated by Clostridium glycolicum infection, resulting in an acute abdomen. The patient clinically improved with antibiotic therapy. A thorough review of the National Institute of Health database revealed that only a small number of cases have been reported since 2007, with the last postsurgical cases documented in 2009 and the last clinical case documented in 2012. Clostridium glycolicum infections have been noted in patients with immunosuppressive conditions or those undergoing medical treatments that compromise immune function. This case was unusual due to the patient being immunocompetent. We suggest that a case of an acute abdomen should consider this organism as an etiological agent.

Keywords: acute abdomen, bacterial infection, clostridium glycolicum, Meckel’s diverticulum, pneumoperitoneum, small bowel obstruction

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Authors: Karim Mohamed Fawzy Ghuiba, Alaa Aldeen Abd Al Hakeem Balbaa, Shams Elbaz

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Objectives: To compare between the effects continuous and pulsed ultrasound on pain and function in patient with knee osteoarthritis. Design: Randomized-Single blinded Study. Participants: 6 patients with knee osteoarthritis with mean age 53.66±3.61years, Altman Grade II or III. Interventions: Subjects were randomly assigned into two groups; Group A received continuous ultrasound and Group B received pulsed ultrasound. Outcome measures: Effects of pulsed and continuous ultrasound were evaluated by pain threshold assessed by visual analogue scale (VAS) scores and function assessed by the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) scores. Results: There was no significant decrease in VAS and WOMAC scores in patients treated with pulsed or continuous ultrasound; and there were no significant differences between both groups. Conclusion: there is no difference between the effects of pulsed and continuous ultrasound in pain relief or functional outcome in patients with knee osteoarthritis.

Keywords: knee osteoarthritis, pulsed ultrasound, ultrasound therapy, continuous ultrasound

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Authors: Joanna Maj

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Body machine interfaces (BMIs) afford users a non-invasive way coordinate movement. Vibrotactile stimulation has been incorporated into BMIs to allow feedback in real-time and guide movement control to benefit patients with cognitive deficits, such as stroke survivors. To advance research in this area, we examined vibrational discrimination thresholds at four body locations to determine suitable application sites for future multi-channel BMIs using vibration cues to guide movement planning and control. Twelve healthy adults had a pair of small vibrators (tactors) affixed to the skin at each location: forearm, shoulders, torso, and knee. A "standard" stimulus (186 Hz; 750 ms) and "probe" stimuli (11 levels ranging from 100 Hz to 235 Hz; 750 ms) were delivered. Probe and test stimulus pairs could occur sequentially or simultaneously (timing). Participants verbally indicated which stimulus felt more intense. Stimulus order was counterbalanced across tactors and body locations. Probabilities that probe stimuli felt more intense than the standard stimulus were computed and fit with a cumulative Gaussian function; the discrimination threshold was defined as one standard deviation of the underlying distribution. Threshold magnitudes depended on stimulus timing and location. Discrimination thresholds were better for stimuli applied sequentially vs. simultaneously at the torso as well as the knee. Thresholds were small (better) and relatively insensitive to timing differences for vibrations applied at the shoulder. BMI applications requiring multiple channels of simultaneous vibrotactile stimulation should therefore consider the shoulder as a deployment site for a vibrotactile BMI interface.

Keywords: electromyography, electromyogram, neuromuscular disorders, biomedical instrumentation, controls engineering

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Authors: Meiling Yu, Nadia Rouatbi, Khuloud T. Al-Jamal

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Background: Treatment of neurological disorders with modern medical and surgical approaches remains difficult. Gene therapy, allowing the delivery of genetic materials that encodes potential therapeutic molecules, represents an attractive option. The treatment of brain diseases with gene therapy requires the gene-editing tool to be delivered efficiently to the central nervous system. In this study, we explored the efficiency of different delivery routes, namely intravenous (i.v.), intra-cranial (i.c.), and intra-nasal (i.n.), to deliver stable nucleic acid-lipid particles (SNALPs) containing gene-editing tools namely Cas9 mRNA and sgRNA encoding for GFP as a reporter protein. We hypothesise that SNALPs can reach the brain and perform gene-editing to different extents depending on the administration route. Intranasal administration (i.n.) offers an attractive and non-invasive way to access the brain circumventing the blood–brain barrier. Successful delivery of gene-editing tools to the brain offers a great opportunity for therapeutic target validation and nucleic acids therapeutics delivery to improve treatment options for a range of neurodegenerative diseases. In this study, we utilised Rosa26-Cas9 knock-in mice, expressing GFP, to study brain distribution and gene-editing efficiency of SNALPs after i.v.; i.c. and i.n. routes of administration. Methods: Single guide RNA (sgRNA) against GFP has been designed and validated by in vitro nuclease assay. SNALPs were formulated and characterised using dynamic light scattering. The encapsulation efficiency of nucleic acids (NA) was measured by RiboGreen™ assay. SNALPs were incubated in serum to assess their ability to protect NA from degradation. Rosa26-Cas9 knock-in mice were i.v., i.n., or i.c. administered with SNALPs to test in vivo gene-editing (GFP knockout) efficiency. SNALPs were given as three doses of 0.64 mg/kg sgGFP following i.v. and i.n. or a single dose of 0.25 mg/kg sgGFP following i.c.. knockout efficiency was assessed after seven days using Sanger Sequencing and Inference of CRISPR Edits (ICE) analysis. In vivo, the biodistribution of DiR labelled SNALPs (SNALPs-DiR) was assessed at 24h post-administration using IVIS Lumina Series III. Results: Serum-stable SNALPs produced were 130-140 nm in diameter with ~90% nucleic acid loading efficiency. SNALPs could reach and stay in the brain for up to 24h following i.v.; i.n. and i.c. administration. Decreasing GFP expression (around 50% after i.v. and i.c. and 20% following i.n.) was confirmed by optical imaging. Despite the small number of mice used, ICE analysis confirmed GFP knockout in mice brains. Additional studies are currently taking place to increase mice numbers. Conclusion: Results confirmed efficient gene knockout achieved by SNALPs in Rosa26-Cas9 knock-in mice expressing GFP following different routes of administrations in the following order i.v.= i.c.> i.n. Each of the administration routes has its pros and cons. The next stages of the project involve assessing gene-editing efficiency in wild-type mice and replacing GFP as a model target with therapeutic target genes implicated in Motor Neuron Disease pathology.

Keywords: CRISPR, nanoparticles, brain diseases, administration routes

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Authors: Gomes C. C. Izabel, Lanzotti B. Rafaela, Orlandi S. Fabiana

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Chronic Kidney Disease is considered a serious public health problem. The exploitation of resilience has been guided by studies conducted in various contexts, especially in hemodialysis, since the impact of diagnosis and restrictions produced during the treatment process because, despite advances in treatment, remains the stigma of the disease and the feeling of pain, hopelessness, low self-esteem and disability. The objective was to evaluate the level of resilience of patients in chronic renal dialysis. This is a descriptive, correlational, cross and quantitative research. The sample consisted of 100 patients from a Renal Replacement Therapy Unit in the countryside of São Paulo. For data collection were used the characterization instrument of Participants and the Resilience Scale. There was a predominance of males (70.0%) were Caucasian (45.0%) and had completed elementary education (34.0%). The average score obtained through the Resilience Scale was 131.3 (± 20.06) points. The resiliency level submitted may be considered satisfactory. It is expected that this study will assist in the preparation of programs and actions in order to avoid possible situations of crises faced by chronic renal patients.

Keywords: hemodialysis units, renal dialysis, renal insufficiency chronic, resilience psychological

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Authors: Sina Modares Ahmadi, Mohamad Reza Ghazavi, Mandana Sheikhzad

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Squeeze film damper systems (SFD) are often used in machines with high rotational speed to reduce non-periodic behavior by creating external damping. These types of systems are frequently used in aircraft gas turbine engines. There are some structural parameters which are of great importance in designing these kinds of systems, such as oil film thickness, C, and outer race mass, mo. Moreover, there is a crucial parameter associated with manufacturing process, under the title of waviness. Geometric imperfections are often called waviness if its wavelength is much longer than Hertzian contact width which is a considerable source of vibration in ball bearings. In this paper, a system of a flexible rotor and two ball bearings with floating ring squeeze film dampers and consideration of waviness has been modeled and solved by a numerical integration method, namely Runge-Kutta method to investigate the dynamic response of the system. The results show that by increasing the number of wave lobes, which is due to inappropriate manufacturing, non- periodic and chaotic behavior increases. This result reveals the importance of manufacturing accuracy. Moreover, as long as C< 1.5×10-4 m, by increasing the oil film thickness, unwanted vibrations and non-periodic behavior of the system have been reduced, On the other hand, when C>1.5×10-4 m, increasing the outer oil film thickness results in the increasing chaotic and non-periodic responses. This result shows that although the presence of oil film results in reduction the non-periodic and chaotic behaviors, but the oil film has an optimal thickness. In addition, with increasing mo, the disc displacement amplitude increases. This result reveals the importance of utilizing light materials in manufacturing the squeeze film dampers.

Keywords: squeeze-film damper, waviness, ball bearing, bifurcation

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Authors: Purwati, Sony Wibisono, Ari Sutjahjo, Askandar T. J., Fedik A. Rantam

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Diabetes mellitus type 2 (T2DM), also known as hyperglycemia, results from insulin resistance and relative insulin deficiency. Diabetes mellitus is the main cause of premature death, particularly among individuals under the age of 70 years old. Mesenchymal stem cells (MSCs) can release bioactive molecules that promote tissue repair and regeneration. Hence, in this research, we evaluated the potential of autologous adipose-derived mesenchymal stem cells (AD-MSCs) in 40 patients of phase I clinical trial in T2DM with various ages between 30-79 years. AD-MSCs are transferred through catheterization. MSCs were validated by measures of CD105+ and CD34- expression. The result showed that after AD-MSCs transplantation, blood glucose levels (fasting and 2-hour postprandial) and insulin levels were significantly decreasing. Besides that, the level of HbA1c significantly decreased after three months of AD-MSCs injection and increasing level of c-peptide after injection. Thus, we conclude that AD-MSCs injection has the potential for T2DM therapy.

Keywords: glucose, hyperglycemia, MSCs, T2DM

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Authors: Yahaya Salihu Emeje, Amuchie Austine Anthony

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The topic examined the prospects of entrepreneurship as an emerging dynamic and strategic tool in the upliftment of human and non-human resources in the Nigerian university system, with a view of showcasing the abundant positive impact, on the Nigerian University system in particular and Nigerian economy at large. It is end at bringing out the benefits of entrepreneurship in the university system which includes, namely cultivating the culture of enterprise in University system; improvement in the quality and quantity of both human and non-human resources; innovative and creative methods of production; new employment strategies in the University system; improved sources of internal generated revenue; entrepreneurship as the culture of sustainability within and outside the university system. Secondary data was used in analyzing entrepreneurship as a productivity tool in the Nigeria University system. From the findings, the university system could be enriched through innovative ideas and technical revenue and employment generation; sustainable financial and economic base; university autonomy and improved international ranking of Nigerian Universities system; therefore, recommended that entrepreneurship is necessary therapy for reviving the ailing, Nigerian universities system.

Keywords: entrepreneurship, strategic, productivity, universities

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Authors: Mohammadamin Esmaeilzadehazimi, Morteza Shayan Arani, Mohammad Toorani, Aouni Lakis

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This study uses a hybrid finite element method to predict the dynamic behavior of both fully and partially-filled truncated conical shells stiffened with ring stiffeners. The method combines classical shell theory and the finite element method, and employs displacement functions derived from exact solutions of Sanders' shell equilibrium equations for conical shells. The shell-fluid interface is analyzed by utilizing the velocity potential, Bernoulli's equation, and impermeability conditions to determine an explicit expression for fluid pressure. The equations of motion presented in this study apply to both conical and cylindrical shells. This study presents the first comparison of the method applied to ring-stiffened shells with other numerical and experimental findings. Vibration frequencies for conical shells with various boundary conditions and geometries in a vacuum and filled with water are compared with experimental and numerical investigations, achieving good agreement. The study thoroughly investigates the influence of geometric parameters, stiffener quantity, semi-vertex cone angle, level of water filled in the cone, and applied boundary conditions on the natural frequency of fluid-loaded ring-stiffened conical shells, and draws some useful conclusions. The primary advantage of the current method is its use of a minimal number of finite elements while achieving highly accurate results.

Keywords: finite element method, fluid–structure interaction, conical shell, natural frequency, ring-stiffener

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Authors: Eun-Joong Kim, Sankarprasad Bhuniya, Hyunseung Lee, Hyun Min Kim, Chaejoon Cheong, Su-khendu Maiti, Kwan Soo Hong, Jong Seung Kim

Abstract:

Metastatic cancers have historically been difficult to treat. However, metastatic tumors have been found to have high levels of reactive oxygen species such as hydrogen peroxide (H2O2), supporting the hypothesis that a prodrug could be activated by intracellular H2O2 and lead to a potential anti-metastatic therapy. In this study, prodrug 7 was designed to be activated by H2O2-mediated boronate oxidation, resulting in activation of the fluorophore for detection and release of the therapeutic agent, SN-38. Drug release from prodrug 7 was investigated by monitoring fluorescence after addition of H2O2 to the cancer cells. Prodrug 7 activated by H2O2 selectively inhibited tumor cell growth. Furthermore, intratracheally administered prodrug 7 showed effective anti-tumor activity in a mouse model of metastatic lung disease. Thus, this H2O2-responsive prodrug has therapeutic potential as a novel treatment for metastatic cancer via cellular imaging with fluorescence as well as selective release of the anti-cancer drug, SN-38.

Keywords: hydrogen peroxide, prodrug, metastatic tumors, fluorescence

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Authors: Huan Peng, Chenye Zeng, Zhao Wang

Abstract:

Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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Authors: Abiodun Amusan, Olugbenga Akinola, Kazeem Akano, María Hernández-Castañeda, Jenna Dick, Akintunde Sowunmi, Geoffrey Hart, Grace Gbotosho

Abstract:

Introduction: Artemisinin-based Combination Therapy (ACTs) is the cornerstone malaria treatment option in most malaria-endemic countries. Unfortunately, the malaria control effort is constantly being threatened by resistance of Plasmodium falciparum to ACTs. The recent evidence of artemisinin resistance in East Africa and its possibility of spreading to other African regions portends an imminent health catastrophe. This study aimed at evaluating the occurrence, prevalence, and influence of artemisinin-resistance markers on treatment outcomes in Ibadan before and after post-adoption of artemisinin combination therapy (ACTs) in Nigeria in 2005. Method: The study involved day zero dry blood spot (DBS) obtained from malaria patients during retrospective (2000-2005) and prospective (2021) studies. A cohort in the prospective study received oral dihydroartemisinin-piperaquine and underwent a 42-day follow-up to observe treatment outcomes. Genomic DNA was extracted from the DBS samples using a QIAamp blood extraction kit. Fragments of P. falciparum kelch13 (Pfkelch13), P. falciparum coronin (Pfcoronin), P. falciparum multidrug resistance 2 (PfMDR2), and P. falciparum chloroquine resistance transporter (PfCRT) genes were amplified and sequenced on a sanger sequencing platform to identify artemisinin resistance-associated mutations. Mutations were identified by aligning sequenced data with reference sequences obtained from the National Center for Biotechnology Information. Data were analyzed using descriptive statistics and student t-tests. Results: Mean parasite clearance time (PCT) and fever clearance time (FCT) were 2.1 ± 0.6 days (95% CI: 1.97-2.24) and 1.3 ± 0.7 days (95% CI: 1.1-1.6) respectively. Four mutations, K189T [34/53(64.2%)], R255K [2/53(3.8%)], K189N [1/53(1.9%)] and N217H [1/53(1.9%)] were identified within the N-terminal (Coiled-coil containing) domain of Pfkelch13. No artemisinin resistance-associated mutation usually found within the β-propeller domain of the Pfkelch13 gene was found in these analyzed samples. However, K189T and R255K mutations showed a significant correlation with longer parasite clearance time in the patients (P<0.002). The observed Pfkelch13 gene changes did not influence the baseline mean parasitemia (P = 0.44). P76S [17/100 (17%)] and V62M [1/100 (1%)] changes were identified in the Pfcoronin gene fragment without any influence on the parasitological parameters. No change was observed in the PfMDR2 gene, while no artemisinin resistance-associated mutation was found in the PfCRT gene. Furthermore, a sample each in the retrospective study contained the Pfkelch13 K189T and Pfcoronin P76S mutations. Conclusion: The study revealed absence of genetic-based evidence of artemisinin resistance in the study population at the time of study. The high frequency of K189T Pfkelch13 mutation and its correlation with increased parasite clearance time in this study may depict geographical variation of resistance mediators and imminent artemisinin resistance, respectively. The study also revealed an inherent potential of parasites to harbour drug-resistant genotypes before the introduction of ACTs in Nigeria.

Keywords: artemisinin resistance, plasmodium falciparum, Pfkelch13 mutations, Pfcoronin

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Authors: An Guo, Hieyong Jeong, Tianyi Wang, Na Li, Yuko Ohno

Abstract:

Acupuncture, known as sensory simulation, has been used to treat various disorders for thousands of years. However, present studies had not addressed approaches for noninvasive measurement in order to evaluate therapeutic effect of acupuncture. The purpose of this study is to propose a noninvasive method to evaluate acupuncture by measuring facial temperature through thermal image. Three human subjects were recruited in this study. Each subject received acupuncture therapy for 30 mins. Acupuncture needles (Ø0.16 x 30 mm) were inserted into Baihui point (DU20), Neiguan points (PC6) and Taichong points (LR3), acupuncture needles (Ø0.18 x 39 mm) were inserted into Tanzhong point (RN17), Zusanli points (ST36) and Yinlingquan points (SP9). Facial temperature was recorded by an infrared thermometer. Acupuncture therapeutic effect was compared pre- and post-acupuncture. Experiment results demonstrated that facial temperature changed according to acupuncture therapeutic effect. It was concluded that proposed method showed high potential to evaluate acupuncture by noninvasive measurement of facial temperature.

Keywords: acupuncture, facial temperature, noninvasive evaluation, thermal image

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Authors: M. Chaichanyut, S. Tungjitkusolmun

Abstract:

This paper is concerned with microwave (MW) ablation for a liver cancer tissue by using helix antenna. The antenna structure supports the propagation of microwave energy at 2.45 GHz. A 1½ turn spiral catheter-based microwave antenna applicator has been developed. We utilize the three-dimensional finite element method (3D FEM) simulation to analyze where the tissue heat flux, lesion pattern and volume destruction during MW ablation. The configurations of helix antenna where Helix air-core antenna and Helix Dielectric-core antenna. The 3D FEMs solutions were based on Maxwell and bio-heat equations. The simulation protocol was power control (10 W, 300s). Our simulation result, both helix antennas have heat flux occurred around the helix antenna and that can be induced the temperature distribution similar (teardrop). The region where the temperature exceeds 50°C the microwave ablation was successful (i.e. complete destruction). The Helix air-core antenna and Helix Dielectric-core antenna, ablation zone or axial ratios (Widest/length) were respectively 0.82 and 0.85; the complete destructions were respectively 4.18 cm³ and 5.64 cm³.

Keywords: liver cancer, Helix antenna, finite element, microwave ablation

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Authors: Javier Enciso-Benavides, Fredy Fabian, Carlos Castaneda, Luis Alfaro, Alex Choque, Aparicio Aguilar, Javier Enciso

Abstract:

Background: The use of biomarkers in breast cancer diagnosis, therapy, and prognosis has gained increasing interest. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and may cause relapse. Therefore, due to the importance of diagnosis, therapy, and prognosis, several biomarkers that characterize CSCs have been identified; however, in treatment-naïve triple-negative breast tumors, there is an urgent need to identify new biomarkers and therapeutic targets. According to this, the aim of this study was to identify serum proteins associated with cancer stem cells and pluripotency in women with triple-negative breast tumors in order to subsequently identify a biomarker for this type of breast tumor. Material and Methods: Whole blood samples from 12 women with histopathologically diagnosed triple-negative breast tumors were used after obtaining informed consent from the patient. Blood serum was obtained by conventional procedure and frozen at -80ºC. Identification of cancer stem cell-associated proteins was performed by matrix-assisted laser desorption/ionisation-assisted laser desorption/ionisation mass spectrometry (MALDI-TOF MS), protein analysis was obtained using the AB Sciex TOF/TOF™ 5800 system (AB Sciex, USA). Sequences not aligned by ProteinPilot™ software were analyzed by Protein BLAST. Results: The following proteins related to pluripotency and cancer stem cells were identified by MALDI TOF/TOF mass spectrometry: A-chain, Serpin A12 [Homo sapiens], AIEBP [Homo sapiens], Alpha-one antitrypsin, AT {internal fragment} [human, partial peptide, 20 aa] [Homo sapiens], collagen alpha 1 chain precursor variant [Homo sapiens], retinoblastoma-associated protein variant [Homo sapiens], insulin receptor, CRA_c isoform [Homo sapiens], Hydroxyisourate hydrolase [Streptomyces scopuliridis], MUCIN-6 [Macaca mulatta], Alpha-actinin-3 [Chrysochloris asiatica], Polyprotein M, CRA_d isoform, partial [Homo sapiens], Transcription factor SOX-12 [Homo sapiens]. Recommendations: The serum proteins identified in this study should be investigated in the exosome of triple-negative breast cancer stem cells and in the blood serum of women without breast cancer. Subsequently, proteins found only in the blood serum of women with triple-negative breast cancer should be identified in situ in triple-negative breast cancer tissue in order to identify a biomarker to study the evolution of this type of cancer, or that could be a therapeutic target. Conclusions: Eleven cancer stem cell-related serum proteins were identified in 12 women with triple-negative breast cancer, of which MUCIN-6, retinoblastoma-associated protein variant, transcription factor SOX-12, and collagen alpha 1 chain are the most representative and have not been studied so far in this type of breast tumor. Acknowledgement: This work was supported by Proyecto CONCYTEC–Banco Mundial “Mejoramiento y Ampliacion de los Servicios del Sistema Nacional de Ciencia Tecnología e Innovacion Tecnologica” 8682-PE (104-2018-FONDECYT-BM-IADT-AV).

Keywords: triple-negative breast cancer, MALDI TOF/TOF MS, serum proteins, cancer stem cells

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Authors: Qingsong Xiong, Cheng Yuan, Qingzhao Kong, Haibei Xiong

Abstract:

Deep-learning-driven approaches based on vibration responses have attracted larger attention in rapid structural condition assessment while obtaining sufficient measured training data with corresponding labels is relevantly costly and even inaccessible in practical engineering. This study proposes an integrated label propagation network for structural condition assessment, which is able to diffuse the labels from continuously-generating measurements by intact structure to those of missing labels of damage scenarios. The integrated network is embedded with damage-sensitive features extraction by deep autoencoder and pseudo-labels propagation by optimized fuzzy clustering, the architecture and mechanism which are elaborated. With a sophisticated network design and specified strategies for improving performance, the present network achieves to extends the superiority of self-supervised representation learning, unsupervised fuzzy clustering and supervised classification algorithms into an integration aiming at assessing damage conditions. Both numerical simulations and full-scale laboratory shaking table tests of a two-story building structure were conducted to validate its capability of detecting post-earthquake damage. The identifying accuracy of a present network was 0.95 in numerical validations and an average 0.86 in laboratory case studies, respectively. It should be noted that the whole training procedure of all involved models in the network stringently doesn’t rely upon any labeled data of damage scenarios but only several samples of intact structure, which indicates a significant superiority in model adaptability and feasible applicability in practice.

Keywords: autoencoder, condition assessment, fuzzy clustering, label propagation

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Authors: Chuan Yin

Abstract:

Cancer stem cells (CSCs) represent a subpopulation of cancer cells that possess the characteristics associated with normal stem cells. CD133 is a phenotype of melanoma CSCs responsible for melanoma metastasis and drug resistance. Although adriamycin (ADR) is commonly used drug in melanoma therapy, but it is ineffective in the treatment of melanoma CSCs. In this study, we constructed CD133 antibody conjugated ADR immunoliposomes (ADR-Lip-CD133) to target CD133+ melanoma CSCs. The results showed that the immunoliposomes possessed a small particle size (~150 nm), high drug encapsulation efficiency (~90%). After 72 hr treatment on the WM266-4 melanoma tumorspheres, the IC50 values of the drug formulated in ADR-Lip-CD133, ADR-Lip (ADR liposomes) and ADR are found to be 24.42, 57.13 and 59.98 ng/ml respectively, suggesting that ADR-Lip-CD133 was more effective than ADR-Lip and ADR. Significantly, ADR-Lip-CD133 could almost completely abolish the tumorigenic ability of WM266-4 tumorspheres in vivo, and showed the best therapeutic effect in WM266-4 melanoma xenograft mice. It is noteworthy that ADR-Lip-CD133 could selectively kill CD133+ melanoma CSCs of WM266-4 cells both in vitro and in vivo. ADR-Lip-CD133 represent a potential approach in targeting and killing CD133+ melanoma CSCs.

Keywords: cancer stem cells, melanoma, immunoliposomes, CD133

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Authors: Hirowati Ali, Aisyah Ellyanti, Dewi Rusnita, Septelia Inawati Wanandi

Abstract:

Stem cell has been known for its potency to be differentiated in many cells. Recently stem cell has been used for many treatment of degenerative medicine. It is still controversy whether stem cell can be used for therapy or these cells can activate cancer stem cell. SCUBE2 is a novel secreted and membrane-anchored protein which has been reported to its role in better prognosis and inhibition of cancer cell proliferation. Our study aims to observe whether stem cell can up-regulate SCUBE2 gene in MCF7 breast cancer cell line. We used in vitro study using MCF-7 cell treated with stem cell derived from placenta Wharton's jelly which has been known for its stemness and widely used. Our results showed that MCF-7 cell line grows up rapidly in 6-well culture dish. Stem cell was cultured in 6-well dish. After 50%-60% MCF-7 confluence, we co-cultured these cells with stem cells for 24 hours and 48 hours. We hypothesize SCUBE2 gene which is previously known for its higher expression in better prognosis of breast cancer, is up-regulated after stem cells addition in MCF7 culture dishes.

Keywords: breast cancer cells, inhibition of cancer cells, mesenchymal stem cells, SCUBE2

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