Search results for: giant cancer cells

Authors: Kyung Jin Kim, Jiwon Kwak, Jae-Hoon Lee, Soo Suk Lee

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MicroRNAs (miRNA) are a class of endogenous, single-stranded, small, and non-protein coding RNA molecules typically 20-25 nucleotides long. They are thought to regulate the expression of other genes in a broad range by binding to 3’- untranslated regions (3’-UTRs) of specific mRNAs. The detection of miRNAs is very important for understanding of the function of these molecules and in the diagnosis of variety of human diseases. However, detection of miRNAs is very challenging because of their short length and high sequence similarities within miRNA families. So, a simple-to-use, low-cost, and highly sensitive method for the detection of miRNAs is desirable. In this study, we demonstrate a novel bi-directional extension (BDE) assay. In the first step, a specific linear RT primer is hybridized to 6-10 base pairs from the 3’-end of a target miRNA molecule and then reverse transcribed to generate a cDNA strand. After reverse transcription, the cDNA was hybridized to the 3’-end which is BDE sequence; it played role as the PCR template. The PCR template was amplified in an SYBR green-based quantitative real-time PCR. To prove the concept, we used human brain total RNA. It could be detected quantitatively in the range of seven orders of magnitude with excellent linearity and reproducibility. To evaluate the performance of BDE assay, we contrasted sensitivity and specificity of the BDE assay against a commercially available poly (A) tailing method using miRNAs for let-7e extracted from A549 human epithelial lung cancer cells. The BDE assay displayed good performance compared with a poly (A) tailing method in terms of specificity and sensitivity; the CT values differed by 2.5 and the melting curve showed a sharper than poly (A) tailing methods. We have demonstrated an innovative, cost-effective BDE assay that allows improved sensitivity and specificity in detection of miRNAs. Dynamic range of the SYBR green-based RT-qPCR for miR-145 could be represented quantitatively over a range of 7 orders of magnitude from 0.1 pg to 1.0 μg of human brain total RNA. Finally, the BDE assay for detection of miRNA species such as let-7e shows good performance compared with a poly (A) tailing method in terms of specificity and sensitivity. Thus BDE proves a simple, low cost, and highly sensitive assay for various miRNAs and should provide significant contributions in research on miRNA biology and application of disease diagnostics with miRNAs as targets.

Keywords: bi-directional extension (BDE), microRNA (miRNA), poly (A) tailing assay, reverse transcription, RT-qPCR

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Authors: Sami Ayad, Mengshan Lee

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The Sustainable Development Goals (SDGs) were designed to be the best possible blueprint to achieve peace, prosperity, and overall, a better and more sustainable future for the Earth and all its people, and such a blueprint is needed more than ever. The SDGs face many hurdles that will prevent them from becoming a reality, one of such hurdles, arguably, is the chemical pollution and unintended chemical impacts generated through the production of various goods and resources that we consume. Chemical Alternatives Assessment has proven to be a viable solution for chemical pollution management in terms of filtering out hazardous chemicals for a greener alternative. However, the current substitution practice lacks crucial quantitative datasets (exposures and life cycle impacts) to ensure no unintended trade-offs occur in the substitution process. A Chemical Life Cycle Alternative Assessment (CLiCAA) framework is proposed as a reliable and replicable alternative to Life Cycle Based Alternative Assessment (LCAA) as it integrates chemical molecular structure analysis and Chemical Life Cycle Collaborative (CLiCC) web-based tool to fill in data gaps that the former frameworks suffer from. The CLiCAA framework consists of a four filtering layers, the first two being mandatory, with the final two being optional assessment and data extrapolation steps. Each layer includes relevant impact categories of each chemical, ranging from human to environmental impacts, that will be assessed and aggregated into unique scores for overall comparable results, with little to no data. A feasibility study will demonstrate the efficiency and accuracy of CLiCAA whilst bridging both cancer potency and exposure limit data, hoping to provide the necessary categorical impact information for every firm possible, especially those disadvantaged in terms of research and resource management.

Keywords: chemical alternative assessment, LCA, LCAA, CLiCC, CLiCAA, chemical substitution framework, cancer potency data, chemical molecular structure analysis

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Authors: Roni Ramon-Gonen, Amir Dori, Shahar Shelly

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Background and objectives: Healthcare professionals produce abundant textual information in their daily clinical practice. The extraction of insights from all the gathered information, mainly unstructured and lacking in normalization, is one of the major challenges in computational medicine. In this respect, text mining assembles different techniques to derive valuable insights from unstructured textual data, so it has led to being especially relevant in Medicine. Neurological patient’s history allows the clinician to define the patient’s symptoms and along with the result of the nerve conduction study (NCS) and electromyography (EMG) test, assists in formulating a differential diagnosis. Past medical history (PMH) helps to direct the latter. In this study, we aimed to identify relevant PMH, understand which PMHs are common among patients in the referral cohort and documented by the medical staff, and examine the differences by sex and age in a large cohort based on textual format notes. Methods: We retrospectively identified all patients with abnormal NCS between May 2016 to February 2022. Age, gender, and all NCS attributes reports were recorded, including the summary text. All patients’ histories were extracted from the text report by a query. Basic text cleansing and data preparation were performed, as well as lemmatization. Very popular words (like ‘left’ and ‘right’) were deleted. Several words were replaced with their abbreviations. A bag of words approach was used to perform the analyses. Different visualizations which are common in text analysis, were created to easily grasp the results. Results: We identified 5282 unique patients. Three thousand and five (57%) patients had documented PMH. Of which 60.4% (n=1817) were males. The total median age was 62 years (range 0.12 – 97.2 years), and the majority of patients (83%) presented after the age of forty years. The top two documented medical histories were diabetes mellitus (DM) and surgery. DM was observed in 16.3% of the patients, and surgery at 15.4%. Other frequent patient histories (among the top 20) were fracture, cancer (ca), motor vehicle accident (MVA), leg, lumbar, discopathy, back and carpal tunnel release (CTR). When separating the data by sex, we can see that DM and MVA are more frequent among males, while cancer and CTR are less frequent. On the other hand, the top medical history in females was surgery and, after that, DM. Other frequent histories among females are breast cancer, fractures, and CTR. In the younger population (ages 18 to 26), the frequent PMH were surgery, fractures, trauma, and MVA. Discussion: By applying text mining approaches to unstructured data, we were able to better understand which medical histories are more relevant in these circumstances and, in addition, gain additional insights regarding sex and age differences. These insights might help to collect epidemiological demographical data as well as raise new hypotheses. One limitation of this work is that each clinician might use different words or abbreviations to describe the same condition, and therefore using a coding system can be beneficial.

Keywords: abnormal studies, healthcare analytics, medical history, nerve conduction studies, text mining, textual analysis

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Authors: Paras Agarwal

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Background: Initially believed to be rare, metastases to the eye are the most common ocular malignancy. The choroid’s high perfusion rate not only makes it the most susceptible ocular site for tumour seeding, but also promotes its growth. The cancers most frequently responsible for choroidal metastases originate from the breast and lung, although a significant proportion have unidentified primaries at the time of presentation. Case Presentation: This case report describes a 34 year old female presenting to the ophthalmology department with a one month history of painless distorted vision. On fundus examination, she was noted to have bilateral choroidal lesionsand subsequently underwent a comprehensive diagnostic work-up. The patient was diagnosed with metastatic pulmonary adenocarcinoma, despite lacking conventional risk factors. As she was found to have a mutation in EGFR, the patient was commenced on tyrosine-kinase inhibition with afatinib. The choroidal lesions regressed with a significant improvement in visual acuity and a dramatic anatomical reduction of the choroidal masses. Conclusions: Our case demonstrates the importance of considering metastases as a differential diagnosis for choroidal lesions. Appropriate and thorough history-taking, examination and investigations may be required in order to deduce the underlying cause. Our case is unusual in view of the choroidal lesion being the primary manifestation of metastatic lung cancer in a young patient with no known risk factors. Early recognition of choroidal metastases is important as it is often the first sign of tumour dissemination and will prompt earlier treatment with systemic medications such as chemotherapy, immunotherapy, targeted therapy or hormonal therapy. Our case report also demonstrates the efficacy of afatinib for the treatment of choroidal metastases, with morphological and functional improvements observed with regard to the choroidal metastatic tumour.

Keywords: choroidal neoplasm, choroidal naevus, pulmonary adenocarcinoma, metastases, lung cancer

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Authors: Felipe Osorio Ospina, Maria Adelaida Mejia Arango, Esteban Onésimo Vallejo Agudelo, Victoria Lucía Dávila Osorio, Natalia Vargas Grisales, Lina María Martínez Sanchez, Camilo Andrés Agudelo Vélez, Ángela Maria Londoño García, Isabel Cristina Ortiz Trujillo

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Excessive exposure to ultraviolet radiation, has shown to be a risk factor for photodamage, alteration of the immune mechanisms to recognize malignant cells and cutaneous pro-inflamatorios States and skin cancers. Objective: Identify the time of exposure to ultraviolet radiation for the production of chromosomal damage in human lymphocytes. Methodology: We conducted an in vitro study serial, in which samples were taken from heparinized blood of healthy people, who do not submit exposure to agents that could induce chromosomal alterations. The samples were cultured in RPMI-1640 medium containing 10% fetal bovine serum, penicillin and streptomycin antibiotic. Subsequently, they were grouped and exposed to ultraviolet light for 1 to 20 seconds. At the end of the treatments, cytology samples were prepared, and it was colored with Giemsa (5%). Reading was carried out in an optical microscope and 100 metaphases analysed by treatment for posting chromosomal alterations. Each treatment was conducted at three separate times and each became two replicas. Results: We only presented chromosomal alterations in lymphocytes exposed to UV for a groups 1 to 3 seconds (p<0.05). Conclusions: Exposure to ultraviolet radiation generates visible damage in chromosomes from human lymphocytes observed in light microscopy, the highest rates of injury was observed between two and three seconds, and above this value, the reduction in the number of mitotic cells was evident.

Keywords: ultraviolet rays, lymphocytes, chromosome breakpoints, photodamage

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Authors: Felipe Osorio Ospina, Maria Adelaida Mejia Arango, Esteban Onésimo Vallejo Agudelo, Victoria Lucía Dávila Osorio, Natalia Vargas Grisales, Lina María Martínez Sanchez, Camilo Andrés Agudelo Vélez, Ángela Maria Londoño García, Isabel Cristina Ortiz Trujillo

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Excessive exposure to ultraviolet radiation, has shown to be a risk factor for photodamage, alteration of the immune mechanisms to recognize malignant cells and cutaneous pro-inflamatorios states and skin cancers. Objective: To identify the time of exposure to ultraviolet radiation for the production of chromosomal damage in human lymphocytes. Methodology: We conducted an in vitro study serial, in which samples were taken from the heparinized blood of healthy people, who do not submit exposure to agents that could induce chromosomal alterations. The samples were cultured in RPMI-1640 medium containing 10% fetal bovine serum, penicillin, and streptomycin antibiotic. Subsequently, they were grouped and exposed to ultraviolet light for 1 to 20 seconds. At the end of the treatments, cytology samples were prepared, and it was colored with Giemsa (5%). Reading was carried out in an optical microscope and 100 metaphases analysed by treatment for posting chromosomal alterations. Each treatment was conducted at three separate times and each became two replicas. Results: We only presented chromosomal alterations in lymphocytes exposed to UV for groups 1 to 3 seconds (p < 0.05). Conclusions: Exposure to ultraviolet radiation generates visible damage in chromosomes from human lymphocytes observed in light microscopy, the highest rates of injury was observed between two and three seconds, and above this value, the reduction in the number of mitotic cells was evident.

Keywords: chromosome breakpoints, lymphocytes, photodamage, ultraviolet rays

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Authors: B. Samuel Raj, Solomon R. D. Jebakumar

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Microbial fuel cells (MFCs) are an emerging and promising method for achieving sustainable energy since they can remove contaminated organic matter and simultaneously generate electricity. Our approach was driven in three different ways like Bacterial fuel cell, Soil Microbial fuel cell (Soil MFC) and Plant Microbial fuel cell (Plant MFC). Bacterial MFC: Sulphate reducing bacteria (SRB) were isolated and identified as the efficient electricigens which is able to produce ±2.5V (689mW/m2) and it has sustainable activity for 120 days. Experimental data with different MFC revealed that high electricity production harvested continuously for 90 days 1.45V (381mW/m2), 1.98V (456mW/m2) respectively. Biofilm formation was confirmed on the surface of the anode by high content screening (HCS) and scanning electron Microscopic analysis (SEM). Soil MFC: Soil MFC was constructed with low cost and standard Mudwatt soil MFC was purchased from keegotech (USA). Vermicompost soil (V1) produce high energy (± 3.5V for ± 400 days) compared to Agricultural soil (A1) (± 2V for ± 150 days). Biofilm formation was confirmed by HCS and SEM analysis. This finding provides a method for extracting energy from organic matter, but also suggests a strategy for promoting the bioremediation of organic contaminants in subsurface environments. Our Soil MFC were able to run successfully a 3.5V fan and three LED continuously for 150 days. Plant MFC: Amaranthus candatus (P1) and Triticum aestivium (P2) were used in Plant MFC to confirm the electricity production from plant associated microbes, four uniform size of Plant MFC were constructed and checked for energy production. P2 produce high energy (± 3.2V for 40 days) with harvesting interval of two times and P1 produces moderate energy without harvesting interval (±1.5V for 24 days). P2 is able run 3.5V fan continuously for 10days whereas P1 needs optimization of growth conditions to produce high energy.

Keywords: microbial fuel cell, biofilm, soil microbial fuel cell, plant microbial fuel cell

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Authors: Ling-Ling E., Hong-Chen Liu, Dong-Sheng Wang, Fang Su, Xia Wu, Zhan-Ping Shi, Yan Lv, Jia-Zhu Wang

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Objective: The objective of the present study is to evaluate the capacity of a tissue-engineered bone complex of recombinant human bone morphogenetic protein 2 (rhBMP-2) mediated dental pulp stem cells (DPSCs) and nano-hydroxyapatite/collagen/poly(L-lactide)(nHAC/PLA) to reconstruct critical-size alveolar bone defects in New Zealand rabbit. Methods: Autologous DPSCs were isolated from rabbit dental pulp tissue and expanded ex vivo to enrich DPSCs numbers, and then their attachment and differentiation capability were evaluated when cultured on the culture plate or nHAC/PLA. The alveolar bone defects were treated with nHAC/PLA, nHAC/PLA+rhBMP-2, nHAC/PLA+DPSCs, nHAC/PLA+DPSCs+rhBMP-2, and autogenous bone (AB) obtained from iliac bone or were left untreated as a control. X-ray and a polychrome sequential fluorescent labeling were performed post-operatively and the animals were sacrificed 12 weeks after operation for histological observation and histomorphometric analysis. Results: Our results showed that DPSCs expressed STRO-1 and vementin, and favoured osteogenesis and adipogenesis in conditioned media. DPSCs attached and spread well, and retained their osteogenic phenotypes on nHAC/PLA. The rhBMP-2 could significantly increase protein content, alkaline phosphatase (ALP) activity/protein, osteocalcin (OCN) content, and mineral formation of DPSCs cultured on nHAC/PLA. The X-ray graph, the fluorescent, histological observation and histomorphometric analysis showed that the nHAC/PLA+DPSCs+rhBMP-2 tissue-engineered bone complex had an earlier mineralization and more bone formation inside the scaffold than nHAC/PLA, nHAC/PLA+rhBMP-2 and nHAC/PLA+DPSCs, or even autologous bone. Implanted DPSCs contribution to new bone were detected through transfected eGFP genes. Conclutions: Our findings indicated that stem cells existed in adult rabbit dental pulp tissue. The rhBMP-2 promoted osteogenic capability of DPSCs as a potential cell source for periodontal bone regeneration. The nHAC/PLA could serve as a good scaffold for autologous DPSCs seeding, proliferation and differentiation. The tissue-engineered bone complex with nHAC/PLA, rhBMP-2, and autologous DPSCs might be a better alternative to autologous bone for the clinical reconstruction of periodontal bone defects.

Keywords: nano-hydroxyapatite/collagen/poly (L-lactide), dental pulp stem cell, recombinant human bone morphogenetic protein, bone tissue engineering, alveolar bone

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Authors: S. N. Susenburger, D. Boecker

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In the age of Volatility, Uncertainty, Complexity, and Ambiguity (VUCA), where digital transformation is challenging long standing traditional hardware and manufacturing companies, innovation needs a different methodology, strategy, mindset, and culture. What used to be a mindset of scaling per quantity is now shifting to orchestrating ecosystems, platform business models and service bundles. While large corporations are trying to mimic the nimbleness and versatile mindset of startups in the core of their digital strategies, they’re at the frontier of facing one of the largest organizational and cultural changes in history. This paper elaborates on how a manufacturing giant transformed its Corporate Information Technology (IT) to enable digital and Internet of Things (IoT) business while establishing the mindset and the approaches of the Innovation Inside-Out/Outside-In Strategy. It gives insights into the core elements of an innovation culture and the tactics and methodologies leveraged to support the cultural shift and transformation into an IoT company. This paper also outlines the core elements for an innovation culture and how the persona 'Connected Engineer' thrives in the digital innovation environment. Further, it explores how tapping domain-focused ecosystems in vibrant innovative cities can be used as a part of the strategy to facilitate partner co-innovation. Therefore, findings from several use cases, observations and surveys led to conclusion for the strategy tandem of Innovation Inside-Out/Outside-In. The findings indicate that it's crucial in which phases and maturity level the Innovation Inside-Out/Outside-In Strategy is activated: cultural aspects of the business and the regional ecosystem need to be considered, as well as cultural readiness from management and active contributors. The 'not invented here syndrome' is a barrier of large corporations that need to be addressed and managed to successfully drive partnerships, as well as embracing co-innovation and a mindset shifting away from physical products toward new business models, services, and IoT platforms. This paper elaborates on various methodologies and approaches tested in different countries and cultures, including the U.S., Brazil, Mexico, and Germany.

Keywords: innovation management, innovation culture, innovation methodologies, digital transformation

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Authors: Maria Del Carmen Millan-Linares, Ana Lemus Conejo, Rocio Toscano, Alvaro Villanueva, Francisco Millan, Justo Pedroche, Sergio Montserrat-De La Paz

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GPETAFLR (Glycine-Proline-Glutamine-Threonine-Alanine-Phenylalanine-Leucine-Arginine) is a peptide isolated from Lupinus angustifolius L. protein hydrolysate (LPH). Herein, the effect of this peptide was investigated in two different models of neuroinflammation: in the immortalized murine microglia cell line BV-2 and in a high-fat-diet-induced obesity mouse model. Methods and Results: Effects of GPETAFLR on neuroinflammation were evaluated by RT-qPCR, flow cytometry, and ELISA techniques. In BV-2 microglial cells, Lipopolysaccharides (LPS) enhanced the release of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) whereas GPETAFLR decreased pro-inflammatory cytokine levels and increased the release of the anti-inflammatory cytokine IL-10 in BV2 microglial cells. M1 (CCR7 and iNOS) and M2 (Arg-1 and Ym-1) polarization markers results showed how the GPETAFLR octapeptide was able to decrease M1 polarization marker expression and increase the M2 polarization marker expression compared to LPS. Animal model results indicate that GPETAFLR has an immunomodulatory capacity, both decreasing pro-inflammatory cytokine IL-6 and increasing the anti-inflammatory cytokine IL-10 in brain tissue. Polarization markers in the brain tissue were also modulated by GPETAFLR that decreased the pro-inflammatory expression (M1) and increased the anti-inflammatory expression (M2). Conclusion: Our results suggest that GPETAFLR isolated from LPH has significant potential for management of neuroinflammatory conditions and offer benefits derived from the consumption of Lupinus angustifolius L. in the prevention of neuroinflammatory-related diseases.

Keywords: GPETAFLR peptide, BV-2 cell line, neuroinflammation, cytokines, high-fat-diet

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Authors: Jayita Mukhopadhyay

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Even though more than six decades has passed since the death of India’s iconic thinker and mass leader Mahatma Gandhi, the world besieged by terrorism may still take a leaf out of his philosophical discourse on non-violence and attempt to turn his theory into praxis to save mankind. The greatest soul world has ever produced, a man of divine fire, an apostle of peace and non-violence, a revolutionary, a visionary, a social reformer and deliverer of the downtrodden, Father of the nation, these and numerous other epithets have been used by eminent personalities and scholars while describing Mahatma Gandhi. Gandhi was a relentless fighter and mass mobiliser who awakened a sleeping giant, the common men and women of India, shook them out of their docile, fatalistic mould, invigorated them with his doctrine of ahimsa and satyagraha (non violence and strict adherence to truth), instilled in them nationalist zeal and patriotic fervour and turned them into determined, steadfast freedom fighters. Under his leadership, the national liberation movement got a new life and ultimately succeeded in ending the era of foreign domination. And he did all these while resisting a natural tendency of his people to respond violently to unspeakable violence and atrocities unleashed by the colonial British administration desperate to keep India in its empire. In this paper, an attempt will be made to unravel Gandhi’s elucidation of the concept of non-violent resistance, along with non-cooperation and civil disobedience and their actual application through political practices which succeeded in capturing the imagination of not only India’s teeming millions but the entire world. The methodology of analytical study will be used as Gandhi’s own writings and those by noted scholars on Gandhi will be examined extensively to establish contemporary relevance of his thought, his invaluable guidelines about how to cope with poverty, inequality, exploitation, repression and marginalization of some sections of society and resultant radicalization of some disturbed members of human race, the very conditions which spawn terrorism in today’s world.

Keywords: India, non cooperation, non violence, terrorism

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Authors: F. Ruiz-Navarro, M. Matzner, G. Kobinia

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Background: Cerebral palsy (CP) encompasses the largest group of childhood movement disorders, the patterns and severity varies widely. Today, the management focuses only on a rehabilitation therapy that tries to secure the functions remained and prevents complications. However the treatments are not aimed to cure the disease. Stem cells (SCs) transplant via intrathecal is a new approach to the disease. Method: Our aim was to performed a pilot study under the condition of unproven treatment on clinical practice to assessed the safety and efficacy of Neuron Point-of-care Stem cell Therapy (N-POCST), an ambulatory procedure of autologous bone marrow derived SCs (BM-SCs) harvested from the posterior superior iliac crest undergo an on-site cell separation for intrathecal infusion via lumbar puncture. Results: 82 patients were treated in a period of 28 months, with a follow-up after 6 months. They had a mean age of 6,2 years old and male predominance (65,9%). Our preliminary results show that: A. No patient had any major side effects, B. Only 20% presented mild headache due to LP, C. 53% of the patients had an improvement in spasticity, D. 61% improved the coordination abilities, 23% improved the motor function, 15% improved the speech, 23% reduced the number of convulsive events with the same doses or less doses of anti-convulsive medication and 94% of the patients report a subjective general improvement. Conclusions: These results support previous worldwide publications that described the safety and effectiveness of autologous BM-SCs transplant for patients wit CP.

Keywords: autologous transplant, cerebral palsy, point of care, childhood movement disorders

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Authors: Hana Al-Baghaoi, Kumar Shiva Gubbiyappa, Mayuren Candasamy, Kiruthiga Perumal Vijayaraman

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Acne is a chronic inflammatory disease of the sebaceous glands characterized by areas of skin with seborrhea, comedones, papules, pustules, nodules, and possibly scarring. Propionibacterium acnes (P. acnes), plays a key role in the pathogenesis of acne. Their colonization and proliferation trigger the host’s inflammatory response leading to the production of pro-inflammatory cytokines such as interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α). The usage of honey and natural compounds to treat skin ailments has strong support in the current trend of drug discovery. The present study was carried out evaluate antimicrobial and anti-inflammatory potential of Doani Sidr honey and its fractions against P. acnes and to screen madecassoside alone and in combination with fractions of honey. The broth dilution method was used to assess the antibacterial activity. Also, ultra structural changes in cell morphology were studied before and after exposure to Sidr honey using transmission electron microscopy (TEM). The three non-toxic concentrations of the samples were investigated for suppression of cytokines IL 8 and TNF α by testing the cell supernatants in the co-culture of the human peripheral blood mononuclear cells (hPBMCs) heat killed P. acnes using enzyme immunoassay kits (ELISA). Results obtained was evaluated by statistical analysis using Graph Pad Prism 5 software. The Doani Sidr honey and polysaccharide fractions were able to inhibit the growth of P. acnes with a noteworthy minimum inhibitory concentration (MIC) value of 18% (w/v) and 29% (w/v), respectively. The proximity of MIC and MBC values indicates that Doani Sidr honey had bactericidal effect against P. acnes which is confirmed by TEM analysis. TEM images of P. acnes after treatment with Doani Sidr honey showed completely physical membrane damage and lysis of cells; whereas non honey treated cells (control) did not show any damage. In addition, Doani Sidr honey and its fractions significantly inhibited (> 90%) of secretion of pro-inflammatory cytokines like TNF α and IL 8 by hPBMCs pretreated with heat-killed P. acnes. However, no significant inhibition was detected for madecassoside at its highest concentration tested. Our results suggested that Doani Sidr honey possesses both antimicrobial and anti-inflammatory effects against P. acnes and can possibly be used as therapeutic agents for acne. Furthermore, polysaccharide fraction derived from Doani Sidr honey showed potent inhibitory effect toward P. acnes. Hence, we hypothesize that fraction prepared from Sidr honey might be contributing to the antimicrobial and anti-inflammatory activity. Therefore, this polysaccharide fraction of Doani Sidr honey needs to be further explored and characterized for various phytochemicals which are contributing to antimicrobial and anti-inflammatory properties.

Keywords: Doani sidr honey, Propionibacterium acnes, IL-8, TNF alpha

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Authors: Grigoria Athanasaki, Veerarajan Vimala, A. M. Kannan, Louis Cindrella

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Energy usage has been increased throughout the years, leading to severe environmental impacts. Since the majority of the energy is currently produced from fossil fuels, there is a global need for clean energy solutions. Proton Exchange Membrane Fuel Cells (PEMFCs) offer a very promising solution for transportation applications because of their solid configuration and low temperature operations, which allows them to start quickly. One of the main components of PEMFCs is the Gas Diffusion Layer (GDL), which manages water and gas transport and shows direct influence on the fuel cell performance. In this work, a novel dual-layer GDL with gradient porosity was prepared, using polyethylene glycol (PEG) as pore former, to improve the gas diffusion and water management in the system. The microporous layer (MPL) of the fabricated GDL consists of carbon powder PUREBLACK, sodium dodecyl sulfate as a surfactant, 34% wt. PTFE and the gradient porosity was created by applying one layer using 30% wt. PEG on the carbon substrate, followed by a second layer without using any pore former. The total carbon loading of the microporous layer is ~ 3 mg.cm-2. For the assembly of the catalyst layer, Nafion membrane (Ion Power, Nafion Membrane NR211) and Pt/C electrocatalyst (46.1% wt.) were used. The catalyst ink was deposited on the membrane via microspraying technique. The Pt loading is ~ 0.4 mg.cm-2, and the active area is 5 cm2. The sample was ex-situ characterized via wetting angle measurement, Scanning Electron Microscopy (SEM), and Pore Size Distribution (PSD) to evaluate its characteristics. Furthermore, for the performance evaluation in-situ characterization via Fuel Cell Testing using H2/O2 and H2/air as reactants, under 50, 60, 80, and 100% relative humidity (RH), took place. The results were compared to a single layer GDL, fabricated with the same carbon powder and loading as the dual layer GDL, and a commercially available GDL with MPL (AvCarb2120). The findings reveal high hydrophobic properties of the microporous layer of the GDL for both PUREBLACK based samples, while the commercial GDL demonstrates hydrophilic behavior. The dual layer GDL shows high and stable fuel cell performance under all the RH conditions, whereas the single layer manifests a drop in performance at high RH in both oxygen and air, caused by catalyst flooding. The commercial GDL shows very low and unstable performance, possibly because of its hydrophilic character and thinner microporous layer. In conclusion, the dual layer GDL with PEG appears to have improved gas diffusion and water management in the fuel cell system. Due to its increasing porosity from the catalyst layer to the carbon substrate, it allows easier access of the reactant gases from the flow channels to the catalyst layer, and more efficient water removal from the catalyst layer, leading to higher performance and stability.

Keywords: gas diffusion layer, microporous layer, proton exchange membrane fuel cells, relative humidity

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Authors: Cyoung-Huei Huang, Chiu-Li Yeh, Man-Hui Pai, Sung-Ling Yeh

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This study evaluated the effect of different dietary n-6/n-3 polyunsaturated fatty acid (PUFA) ratios on modulating helper T (Th) and regulatory T (Treg) lymphocytes in mice with dextran sulfate sodium (DSS)-induced colitis. There were 3 control and 3 colitis groups in this study. Mice were fed for 24 d with an AIN-93G diet either with soybean oil (S), a mixture of soybean oil and low fish oil content (LF) or high fish oil content (HF). The ratio of n-6/n-3 PUFA in the LF diet was 4:1, and that in the HF diet was 2:1. The control groups drank distilled water while colitis groups provided 2% DSS in drinking water during day 15-19. All mice drank distilled water from day 20-24 for recovery and sacrificed on day 25. The results showed that colitis resulted in higher Th1, Th2, and Th17 and lower Treg percentages in the blood. Also, plasma haptoglobin and proinflammatory chemokines were elevated in colon lavage fluid. Colitic groups with fish oil had lower inflammatory mediators in the plasma and colon lavage fluid. Further, the percentages of Th1, Th2, and Th17 cells in the blood were lower, whereas Treg cell percentages were higher than those in the soybean oil group. The colitis group with n-6/n-3 PUFA ratio 2:1 had more pronounce effects than ratio 4:1. These results suggest that diets with an n-6/n-3 PUFA ratio of 2:1 or 4:1 regulate the Th/Treg balance and attenuate inflammatory mediator production in colitis. Compared to the n-6/n-3 PUFA ratio 4:1, the ratio of 2:1 was more effective in reducing inflammatory reactions in DSS-induced colitis.

Keywords: inflammatory bowel disease, n-3 polyunsaturated fatty acids, helper T lymphocyte, regulatory T lymphocyte

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Authors: Alireza Arab, Morteza Elsa, Amirhossein Moghanian

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In this study, experiments were carried out to achieve a promising multifunctional and modified silicate based bioactive glass (BG). The main aim of the study was investigating the effect of lithium (Li) and magnesium (Mg) substitution, on in vitro bioactivity of substituted-58S BG. Moreover, it is noteworthy to state that modified BGs were synthesized in 60SiO₂–(36-x)CaO–4P₂O₅–(x)Li₂O and 60SiO₂–(36-x)CaO–4P₂O₅–(x)MgO (where x = 0, 5, 10 mol.%) quaternary systems, by sol-gel method. Their performance was investigated through different aspects such as biocompatibility, antibacterial activity as well as their effect on alkaline phosphatase (ALP) activity, and proliferation of MC3T3 cells. The antibacterial efficiency was evaluated against methicillin-resistant Staphylococcus aureus bacteria. To do so, CaO was substituted with Li₂O and MgO up to 10 mol % in 58S-BGs and then samples were immersed in simulated body fluid up to 14 days and then, characterized by X-ray diffraction, Fourier transform infrared spectroscopy, inductively coupled plasma atomic emission spectrometry, and scanning electron microscopy. Results indicated that this modification led to a retarding effect on in vitro hydroxyapatite (HA) formation due to the lower supersaturation degree for nucleation of HA compared with 58s-BG. Meanwhile, magnesium revealed further pronounced effect. The 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and ALP analysis illustrated that substitutions of both Li₂O and MgO, up to 5 mol %, had increasing effect on biocompatibility and stimulating proliferation of the pre-osteoblast MC3T3 cells in comparison to the control specimen. Regarding to bactericidal efficiency, the substitution of either Li or Mg for Ca in the 58s BG composition led to statistically significant difference in antibacterial behaviors of substituted-BGs. Meanwhile, the sample containing 5 mol % CaO/Li₂O substitution (BG-5L) was selected as a multifunctional biomaterial in bone repair/regeneration due to the improved biocompatibility, enhanced ALP activity and antibacterial efficiency among all of the synthesized L-BGs and M-BGs.

Keywords: alkaline, alkaline earth, bioactivity, biomedical applications, sol-gel processes

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Authors: Ahmed Atwa, Ashraf Hafez, Mohamed Abdelhameed, Adel Nabeeh, Mohamed Dawaba, Tamer Helmy

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Introduction and Objective: Tumour staging and grading do not usually reflect the future behavior of Wilms' tumor (WT) regarding mortality. Therefore, in this study, P53, Ki67 and cyclin A immunohistochemistry were used in a trial to predict WT cancer-specific survival (CSS). Methods: In this nonconcurrent cohort study, patients' archived data, including age at presentation, gender, history, clinical examination and radiological investigations, were retrieved then the patients were reviewed at the outpatient clinic of a tertiary care center by history-taking, clinical examination and radiological investigations to detect the oncological outcome. Cases that received preoperative chemotherapy or died due to causes other than WT were excluded. Formalin-fixed, paraffin-embedded specimens obtained from the previously preserved blocks at the pathology laboratory were taken on positively charged slides for IHC with p53, Ki67 and cyclin A. All specimens were examined by an experienced histopathologist devoted to the urological practice and blinded to the patient's clinical findings. P53 and cyclin A staining were scored as 0 (no nuclear staining),1 (<10% nuclear staining), 2 (10-50% nuclear staining) and 3 (>50% nuclear staining). Ki67 proliferation index (PI) was graded as low, borderline and high. Results: Of the 75 cases, 40 (53.3%) were males and 35 (46.7%) were females, and the median age was 36 months (2-216). With a mean follow-up of 78.6±31 months, cancer-specific mortality (CSM) occurred in 15 (20%) and 11 (14.7%) patients, respectively. Kaplan-Meier curve was used for survival analysis, and groups were compared using the Log-rank test. Multivariate logistic regression and Cox regression were not used because only one variable (cyclin A) had shown statistical significance (P=.02), whereas the other significant factor (residual tumor) had few cases. Conclusions: Cyclin A IHC should be considered as a marker for the prediction of WT CSS. Prospective studies with a larger sample size are needed.

Keywords: wilms’ tumour, nephroblastoma, urology, survival

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Authors: Hamzeh Alipour, Masoumeh Bagheri, Tahereh Karamzadeh, Abbasali Raz, Kourosh Azizi

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Netrin-A, a protein identified for conducting commissural axons, has a similar role in angiogenesis. In addition, studies have shown that one of the netrin-A receptors is expressed in the growing cells of small capillaries. It will be interesting to study this new group of molecules because their role in wound healing will become clearer in the future due to angiogenesis. The greenbottle blowfly Luciliasericata (L. sericata) larvae are increasingly used in maggot therapy of chronic wounds. This aim of this was the identification of moleculareatures of Netrin-A in L. sericata larvae. Larvae were reared under standard maggotarium conditions. The nucleic acid sequence of L. sericataNetrin-A (LSN-A) was then identified using Rapid Amplification of cDNA Ends (RACE) and Rapid Amplification of Genomic Ends (RAGE). Parts of the Netrin-A gene, including the middle, 3′-, and 5′-ends were identified, TA cloned in pTG19 plasmid, and transferred into DH5ɑ Escherichia coli. Each part was sequenced and assembled using SeqMan software. This gene structure was further subjected to in silico analysis. The DNA of LSN-A was identified to be 2407 bp, while its mRNA sequence was recognized as 2115 bp by Oligo0.7 software. It translated the Netrin-A protein with 704 amino acid residues. Its molecular weight is estimated to be 78.6 kDa. The 3-D structure ofNetrin-A drawn by SWISS-MODEL revealed its similarity to the Netrin-1 of humans with 66.8% identity. The LSN-A protein conduces to repair the myelin membrane in neuronal cells. Ultimately, it can be an effective candidate in neural regeneration and wound healing. Furthermore, our next attempt is to deplore recombinant proteins for use in medical sciences.

Keywords: maggot therapy, netrin-A, RACE, RAGE, lucilia sericata

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Authors: Jinyoung Park, Eun Joo Song

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Introduction: Deubiquitinating enzymes (DUBs) are proteases that cleave ubiquitin or ubiquitin-like modifications on substrates. Deubiquitination could regulate cellular physiology, such as signal transduction, DNA damage and repair, and cell cycle progression. Although more than 100 DUBs are encoded in the human and the importance of DUBs has been realized, the functions of most DUBs are unknown. This study aims to identify the molecular mechanism by which deubiquitinating enzyme USP35 regulates cell cycle progression for the first time. Methods: USP35 RNAi was mainly used to identify the function of USP35 in cell cycle progression. To find substrates of USP35, we analyzed protein-protein interaction using LC-MS. Several biological methods, such as ubiquitination assay, cell synchronization, immunofluorescence, and immunoprecipitation assay were used to investigate the exact mechanism by which USP35 affects successful completion of mitosis. Results: USP35 knockdown caused not only reduction of mitotic cell number but also induction of mitotic cells with abnormal spindle formation. Actually, cell proliferation was decreased by USP35 knockdown. Interestingly, we found that loss of USP35 decreased the stability and expression of Aurora B, a member of chromosomal passenger complex (CPC), and the phosphorylation of its substrate. Indeed, USP35 interacted with Aurora B and deubiquitinated it. In addition, USP35 knockdown induced abnormal localization of Aurora B in mitotic cells. Finally, CDH1-mediated ubiquitination of Aurora B level was rescued by USP35 overexpression, but not inactive form of USP35, USP35 C450A. Discussion: Our findings suggest that USP35 regulates Aurora B-mediated mitotic spindle assembly and G2-M transition by blocking CDH1-induced degradation of Aurora B.

Keywords: USP35, HSP90, Aurora B, cell cycle progression

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Authors: Ercan Karadogan, Fatih Usta

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Auxetic materials have a negative Poisson’s ratio (NPR), which is not often found in nature. They are metamaterials that have potential applications in many engineering fields. Mechanical metamaterials are synthetically designed structures with unusual mechanical properties. These mechanical properties are dependent on the properties of the matrix structure. They have the following special characteristics, i.e., improved shear modulus, increased energy absorption, and intensive fracture toughness. Non-auxetic materials compress transversely when they are stretched. The system naturally is inclined to keep its density constant. The transversal compression increases the density to balance the loss in the longitudinal direction. This study proposes to improve the crushing performance of hybrid auxetic materials. The re-entrant honeycomb structure has been combined with a star honeycomb, an S-shaped unit cell, a double arrowhead, and a structurally hexagonal re-entrant honeycomb by 9 X 9 cells, i.e., the number of cells is 9 in the lateral direction and 9 in the vertical direction. The Finite Element (FE) and experimental methods have been used to determine the compression behavior of the developed hybrid auxetic structures. The FE models have been developed by using Abaqus software. The specimens made of polymer plastic materials have been 3D printed and subjected to compression loading. The results are compared in terms of specific energy absorption and strength. This paper describes the quasi-static crushing behavior of two types of hybrid lattice structures (auxetic + auxetic and auxetic + non-auxetic). The results show that the developed hybrid structures can be useful to control collapse mechanisms and present larger energy absorption compared to conventional re-entrant auxetic structures.

Keywords: auxetic materials, compressive behavior, metamaterials, negative Poisson’s ratio

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Authors: Gi-Hoon Yang, JongHan Ha, MyungGu Yeo, JaeYoon Lee, SeungHyun Ahn, Hyeongjin Lee, HoJun Jeon, YongBok Kim, Minseong Kim, GeunHyung Kim

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Tissue engineering scaffolds must be biocompatible and biodegradable, provide adequate mechanical strength and cell attachment site for proliferation and differentiation. Furthermore, the scaffold morphology (such as pore size, porosity and pore interconnectivity) plays an important role. The electrospinning process has been widely used to fabricate micro/nano-sized fibres. Electrospinning allows for the fabrication of non-woven meshes containing micro- to nano-sized fibers providing high surface-to-volume area for cell attachment. Due to its advantageous characteristics, electrospinning is a useful method for skin, cartilage, bone, and nerve regeneration. In this study, we fabricated PCL scaffolds (SP) consisting of spiral-like struts using 3D melt-plotting system and micro/nanofibers using direct electrospinning writing. By altering the conditions of the conventional melt-plotting method, spiral-like struts were generated. Then, micro/nanofibers were deposited selectively. The control scaffold composed of perpendicular PCL struts was fabricated using the conventional melt-plotting method to compare the cellular activities. The effect on the attached cells (osteoblast-like cells (MG63)) was evaluated depending on the bending instability of the struts. The SP scaffolds showed enhanced biological properties such as initial cell attachment, proliferation and osteogenic differentiation. These results suggest that the SP scaffolds has potential as a bioengineered substitute for soft and hard tissue regeneration.

Keywords: cell attachment, electrospinning, mechanical strength, melt-plotting

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Authors: Mohammed Jarrar, Shalini Behl, Nadia Shaheen, Abeer Fatima, Reem Nasab

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Skin aging is a slow multifactorial process influenced by both internal as well as external factors. Ultra-violet radiations (UV), diet, smoking and personal habits are the most common environmental factors that affect skin aging. Fat contents and fibrous proteins as collagen and elastin are core internal structural components. The direct influence of UV on elastin integrity and health is crucial on aging of skin by time. The deposition of abnormal elastic material is a major marker in a photo-aged skin. Searching for compounds that may protect against cutaneous photo-damage is highly valued. Retinoids and Alpha Hydroxy Acids protective and or repairing effects of UV have been endorsed by some researchers. For consolidating a better understanding of anti and protective effects of such anti-aging agents, we evaluated the combinatory effects of various dosages of lactic acid and retinol on the dermal fibroblasts elastin levels exposed to UV. The UV exposed cells showed significant reduction in the elastin levels. A combination of drugs with a higher concentration of lactic acid (30-35 mM) and a lower concentration of retinol (10-15mg/mL) showed to work better in enhancing elastin concentration in UV exposed cells. We assume this enhancement could be the result of increased tropo-elastin gene expression stimulated by retinol and lactic acid probably repaired the UV irradiated damage by enhancing the amount and integrity of the elastin fibers.

Keywords: alpha hydroxy acid, elastin, retinol, ultraviolet radiations

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Authors: Reva Sharan Thakur, Mrinalini Tiwari, Jyoti das

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Cerebral malaria-associated over expression of pro-inflammatory cytokines and chemokines ultimately results in the up-regulation of adhesion molecules in the brain endothelium leading to sequestration of mature parasitized RBCs in the brain. The high-parasitic load subsequently results in increased mortality or development of neurological symptoms within a week of infection. Studies in the human and experimental cerebral malaria have implicated the breakdown of the integrity of blood-brain barrier during the lethal course of infection, cerebral dysfunction, and fatal organ pathologies that result in multi-organ failure. In the present study, using Plasmodium berghei Anka as a mouse model and in vitro conditions, we have investigated the effect of MSCs to attenuate cerebral malaria pathogenesis by diminishing the effect of inflammation altered organ morphology, reduced parasitemia, and increased survival of the mice. MSCs are also validated for their role in preventing BBB dysfunction and reducing malarial toxins. It was observed that administration of MSCs significantly reduced parasitemia and increased survival in Pb A infected mice. It was further demonstrated that MSCs play a significant role in reversing neurological complexities associated with cerebral malaria. Infusion of MSCs in infected mice decreased hemozoin deposition; oedema, and haemorrhagic lesions in vascular organs. MSCs administration also preserved the integrity of the blood-brain barrier and reduced neural inflammation. Taken together, our results demonstrate the potential of MSCs as an emerging anti-malarial candidate.

Keywords: cerebral malaria, mesenchymal stem cells, erythropoesis, cell death

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Authors: Anne N. Heirman, Song Duimel, Rob van Son, Lisette van der Molen, Richard Dirven, Gyorgi B. Halmos, Julia van Weert, Michiel W.M. van den Brekel

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Objectives: Treatments for head-neck cancer are drastic and often significantly impact the quality of life and appearance of patients. Shared decision-making (SDM) beholds a collaboration between patient and doctor in which the most suitable treatment can be chosen by integrating patient preferences, values, and medical information. SDM has a lot of advantages that would be useful in making difficult treatment choices. The objective of this study was to determine the current level of SDM among patients and head-and-neck surgeons. Methods: Consultations of patients with a non-cutaneous head-and-neck malignancy facing a treatment decision were selected and included. If given informed consent, the consultation was recorded with an audio recorder, and the patient and surgeon filled in a questionnaire immediately after the consultation. The SDM level of the consultation was scored objectively by independent observers who judged audio recordings of the consultation using the OPTION5-scale, ranging from 0% (no SDM) to 100% (optimum SDM), as well as subjectively by patients (using the SDM-Q-9 and Control preference scale) and clinicians (SDM-Q-Doc, modified control preference scale) percentages. Preliminary results: Five head-neck surgeons have each at least seven recorded conversations with different patients. One of them was trained in SDM. The other four had no experience with SDM. Most patients were male (74%), and oropharyngeal carcinoma was the most common diagnosis (41%), followed by oral cancer (33%). Five patients received palliative treatment of which two patients were not treated recording guidelines. At this moment, all recordings are scored by the two independent observers. Analysis of the results will follow soon. Conclusion: The current study will determine to what extent there is a discrepancy between the objective and subjective level of shared decision-making (SDM) during a doctor-patient consultation in Head-and-Neck surgery. The results of the analysis will follow shortly.

Keywords: head-and-neck oncology, patient involvement, physician-patient relations, shared decision making

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Authors: Mahmoud Almasri, Xavier Marjou, Fanny Parzysz

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The demand for services provided by Unmanned Aerial Vehicles (UAVs) is increasing pervasively across several sectors including potential public safety, economic, and delivery services. As the number of applications using UAVs grows rapidly, more and more powerful, quality of service, and power efficient computing units are necessary. Recently, cellular technology draws more attention to connectivity that can ensure reliable and flexible communications services for UAVs. In cellular technology, flying with a high speed and altitude is subject to several key challenges, such as frequent handovers (HOs), high interference levels, connectivity coverage holes, etc. Additional HOs may lead to “ping-pong” between the UAVs and the serving cells resulting in a decrease of the quality of service and energy consumption. In order to optimize the number of HOs, we develop in this paper a Q-learning-based algorithm. While existing works focus on adjusting the number of HOs in a static network topology, we take into account the impact of cells deployment for three different simulation scenarios (Rural, Semi-rural and Urban areas). We also consider the impact of the decision distance, where the drone has the choice to make a switching decision on the number of HOs. Our results show that a Q-learning-based algorithm allows to significantly reduce the average number of HOs compared to a baseline case where the drone always selects the cell with the highest received signal. Moreover, we also propose which hyper-parameters have the largest impact on the number of HOs in the three tested environments, i.e. Rural, Semi-rural, or Urban.

Keywords: drones connectivity, reinforcement learning, handovers optimization, decision distance

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Authors: Lubna Azmi, Ila Shukla, Shyam Sundar Gupta, Padam Kant, Ch. V. Rao

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Gastric ulcer is a major global health threat, and it is the leading cause of stomach cancer death worldwide. Helicobacter pylori bacteriumis the most important etiologic factor for gastric ulcer. This infection is highly pervasive in South Asian developing countries, especially in India, Nepal, Srilanka etc. due to diversification in geographic area. Pathophysiology of gastric mucosal damage associated with non-invasive bacterium has not justified in detail, but it leads to change in histopathology, immunochemistry of the gastric and duodenal reason of host. The mechanism responsible for bacteria tissue tropism and mucosal damage in stomach variance during the disease is not clearly described and understood scientifically in treatment and control of pathogenic organisms. Polyphenols are secondary metabolites of plants and are generally involved in defense against aggression by pathogens. 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one and 1-hydroxy-5,7-dimethoxy-2-naphthalene-carboxaldehyde are polyphenolic compound obtained from popular Indian medicinal plants ghavpatta (ArgeriaspeciosaLinn.f) andBael (Aeglemarmelos) have long been used in traditional Ayurvedic Indian medicine for various diseases. They have promising effects on ulcer, as detailed investigation has made in our laboratory. Therefore, the aim of present study is to explore membrane –dependent morphogenesis of H. pylori and associated apoptosis-mediated cell death. Based on this we analyzed immune gene expression in stomach of experimental animals with H. pylori, using quantitative reverse transcription polymerase chain reaction(q RT-PCR). This revealed rapid induction of prostaglandin, interferon I (INF-I), interferon II (INF-II) and INF-I associated genes in the infected animal. Ultrastructural changes associated with H. pylori will be taken for advanced studies. This investigation shows that the biomarkers eradicate H. pylori bacterium caused gastric ulcer which is a major risk factor for gastric cancer.

Keywords: gastric ulcer, Helicobacter pylori, immunochemistry, polyphenols

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Authors: Howaida I. Abd-Alla, Amal Z. Hassan, Maha Soltan, Atef G. Hanna, Mounir M. El-Safty

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Acokanthera oblongifolia (Apocynaceae) is used for treatment of several infection diseases and is a well-known cardiac glycoside-containing plant. The infusion of their leaves is gargled to treat tonsillitis and is used medicinally to treat snakebites. The total cardiac glycosides content in the leaves was determined by referring to gitoxigenin as a reference compound. Two triterpenes, lup-20(29)-en-3β-ol (1) and oleanolic acid (2); two cardenolides, acovenoside A (3) and acobioside A (4) were isolated from the ethyl acetate extract. Their structures were determined on the basis of spectral analysis. Major constituents isolated from this species were evaluated for cytotoxicity against normal lung cell line (Wi38) and antimicrobial activities against Gram-positive (two strains) and Gram-negative bacteria (four strains), yeast-like fungi (two strains) and fungi (five strains). The minimum inhibitory concentration (MIC) of the compounds was determined using broth microdilution method. Their viral inhibitory effects against avian influenza virus type A (AI-H5N1) and Newcastle disease virus (NDV) in specific pathogen free (SPF) embryonated chicken eggs (ECE), chicken embryo fibroblasts (CEF) and Vero cells were evaluated. The cardenolide (3) showed viral inhibitory effects against AI-H5N1 and NDV in SPF ECE. The two cardenolides isolated have shown potent cytotoxicity against Vero cells. Compound (3) showed potent anti-Gram-negative bacteria activity. These results suggested that acovenoside A might be promising for future antiviral and antimicrobial drug design.

Keywords: Acokanthera, AI-H5N1, Cardenolides, NDV, SPF-ECE, VERO, Wi38 , Microbe

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Authors: Nobuyuki Takemoto, Ai Koyanagi, Masanori Yasuda, Hiroshi Yamamoto

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Background: Fluorescence imaging (FI) is one of the methods to identify sentinel lymph nodes (SLNs). However, the procedure is technically complicated and requires procedural skills, as SLN biopsy must be conducted in dim light conditions. As an improved version of this method, we introduced a combined method (Combined mixed dye and fluorescence; CMF) consisting of indigo carmine blue dye and FI. The direct visualization of SLNs under shadowless surgical light conditions is facilitated by the addition of the blue dye. We compared the SLN detection rates of CMF with that of the indocyanine green (ICG) dye method (ICG-D). Methods: A total of 202 patients with stage ≤ IIA breast cancer who underwent breast conservative therapy with separate incision from January 2004 to February 2017 were reviewed. Details of the two methods are as follows: (1) ICG-D: 2ml of ICG (10mg) was used and the green-stained SLNs were resected via a 3-4cm axillary incision; (2) CMF: A combination of 1ml of ICG (5mg) and 1-3ml of indigo carmine (4-12mg) was used. Using Photodynamic Eye (PDE), a 1.5-2 cm incision was made near the point of disappearance of the fluorescence and SLNs with intermediate color of blue and green were resected. Results: There were 92 ICG-D and 110 CMF cases. CMF resulted in a significantly higher detection rate than ICG-D (96.4% vs. 83.7%; p=0.003). This difference was particularly notable in those aged ≥ 60 years (98.3% vs. 74.3%) and individuals with BMI ≥ 25kg/m2 (90.3% vs. 58.3%). Conclusion: CMF is an effective method to identify SLNs which is safe, efficient, and cost-effective. Furthermore, radiation exposure can be avoided, and it can be performed in institutes without nuclear medicine facilities. CMF achieves a high SLN identification rate, and most of this procedure is feasible under shadowless surgical light conditions. CMF can reliably perform SLN biopsy even in those aged ≥ 60 years and individuals with BMI ≥ 25 kg/m2.

Keywords: sentinel lymph node biopsy, identification rate, indocyanine green (ICG), indigocarmine, fluorescence

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Authors: Öznur Saribaş, Si̇bel Kahraman Çeti̇ntaş

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It is aimed to compare target volume and critical organ doses by using CyberKnife (CK) in accelerated partial breast irradiation (APBI) in patients with early stage breast cancer. Three different virtual plans were made for Iris, fixed and multi-leaf collimator (MLC) for 5 patients who received radiotherapy in the CyberKnife system. CyberKnife virtual plans were created, with 6 Gy per day totaling 30 Gy. Dosimetric parameters for the three collimators were analyzed according to the restrictions in the NSABP-39/RTOG 0413 protocol. The plans ensured critical organs were protected and GTV received 95 % of the prescribed dose. The prescribed dose was defined by the isodose curve of a minimum of 80. Homogeneity index (HI), conformity index (CI), treatment time (min), monitor unit (MU) and doses taken by critical organs were compared. As a result of the comparison of the plans, a significant difference was found for the duration of treatment, MU. However, no significant difference was found for HI, CI. V30 and V15 values of the ipsi-lateral breast were found in the lowest MLC. There was no significant difference between Dmax values for lung and heart. However, the mean MU and duration of treatment were found in the lowest MLC. As a result, the target volume received the desired dose in each collimator. The contralateral breast and contralateral lung doses were the lowest in the Iris. Fixed collimator was found to be more suitable for cardiac doses. But these values did not make a significant difference. The use of fixed collimators may cause difficulties in clinical applications due to the long treatment time. The choice of collimator in breast SBRT applications with CyberKnife may vary depending on tumor size, proximity to critical organs and tumor localization.

Keywords: APBI, CyberKnife, early stage breast cancer, radiotherapy.

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Authors: Anastasia V. Kovaleva, Alena A. Ryabova, Vladimir N. Kasatkin

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Background: The most simple form of entrainment to a sensory (typically auditory) rhythmic stimulus involves perceiving and synchronizing movements with an isochronous beat with one level of periodicity, such as that produced by a metronome. Children with pediatric cancer usually treated with chemo- and radiotherapy. Because of such treatment, psychologists and health professionals declare cognitive and motor abilities decline in cancer patients. The purpose of our study was to measure working memory characteristics with association with audio-motor synchronization tasks, also involved some memory resources, in children with different degrees of central nervous system lesions: posterior fossa tumors, acute lymphoblastic leukemia, and healthy controls. Methods: Our sample consisted of three groups of children: children treated for posterior fossa tumors (PFT-group, n=42, mean age 12.23), children treated for acute lymphoblastic leukemia (ALL-group, n=11, mean age 11.57) and neurologically healthy children (control group, n=36, mean age 11.67). Participants were tested for working memory characteristics with Cambridge Neuropsychological Test Automated Battery (CANTAB). Pattern recognition memory (PRM) and spatial working memory (SWM) tests were applied. Outcome measures of PRM test include the number and percentage of correct trials and latency (speed of participant’s response), and measures of SWM include errors, strategy, and latency. In the synchronization tests, the instruction was to tap out a regular beat (40, 60, 90 and 120 beats per minute) in synchrony with the rhythmic sequences that were played. This meant that for the sequences with an isochronous beat, participants were required to tap into every auditory event. Variations of inter-tap-intervals and deviations of children’s taps from the metronome were assessed. Results: Analysis of variance revealed the significant effect of group (ALL, PFT and control) on such parameters as short-term PRM, SWM strategy and errors. Healthy controls demonstrated more correctly retained elements, better working memory strategy, compared to cancer patients. Interestingly that ALL patients chose the bad strategy, but committed significantly less errors in SWM test then PFT and controls did. As to rhythmic ability, significant associations of working memory were found out only with 40 bpm rhythm: the less variable were inter-tap-intervals of the child, the more elements in memory he/she could retain. The ability to audio-motor synchronization may be related to working memory processes mediated by the prefrontal cortex whereby each sensory event is actively retrieved and monitored during rhythmic sequencing. Conclusion: Our results suggest that working memory, tested with appropriate cognitive methods, is associated with the ability to synchronize movements with rhythmic sounds, especially in sub-second intervals (40 per minute).

Keywords: acute lymphoblastic leukemia (ALL), audio-motor synchronization, posterior fossa tumor, working memory

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