Search results for: tumor antigen

Authors: Sai Maniveer Adapa, Sai Guptha Perla, Adithya Reddy P.

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Thyroid nodules can often be diagnosed with ultrasound imaging, although differentiating between benign and malignant nodules can be challenging for medical professionals. This work suggests a novel approach to increase the precision of thyroid nodule identification by combining machine learning and deep learning. The new approach first extracts information from the ultrasound pictures using a deep learning method known as a convolutional autoencoder. A support vector machine, a type of machine learning model, is then trained using these features. With an accuracy of 92.52%, the support vector machine can differentiate between benign and malignant nodules. This innovative technique may decrease the need for pointless biopsies and increase the accuracy of thyroid nodule detection.

Keywords: thyroid tumor diagnosis, ultrasound images, deep learning, machine learning, convolutional auto-encoder, support vector machine

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Authors: Tanveer Hussain, Misbah Hussain, Masroor Ellahi Babar, Muhammad Traiq Pervez, Fiaz Hussain, Sana Zahoor, Rashid Saif

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Interleukin 2 (IL-2) is a cytokine which is produced by activated T cells, play important role in immune response against antigen. It act in both autocrine and paracrine manner. It can stimulate B cells and various other phagocytic cells like monocytes, lymphokine-activated killer cells and natural killer cells. Acting in autocrine fashion, IL-2 protein plays a crucial role in proliferation of T cells. IL-2 triggers the release of pro and anti- inflammatory cytokines by activating several pathways. In present study, exon 1 of IL-2 gene of four local Pakistani breeds (Dera Din Panah, Beetal, Nachi and Kamori) from two provinces was amplified by using reported Ovine IL-2 primers, yielding PCR product of 501 bp. The sequencing of all samples was done to identify the polymorphisms in amplified region of IL-2 gene. Analysis of sequencing data resulted in identification of one novel nucleotide substitution (T→A) in amplified non-coding region of IL-2 gene. Comparison of IL-2 gene sequence of all four breeds with other goat breeds showed high similarity in sequence. While phylogenetic analysis of our local breeds with other mammals showed that IL-2 is a variable gene which has undergone many substitutions. This high substitution rate can be due to the decreased or increased changed selective pressure. These rapid changes can also lead to the change in function of immune system. This pioneering study of Pakistani goat breeds urge for further studies on immune system of each targeted breed for fully understanding the functional role of IL-2 in goat immunity.

Keywords: interleukin 2, mutational analysis, phylogeny, goat breeds, Pakistan

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Authors: Simin Shahvazi, Sepideh Soltani, Seyed Mehdi Ahmadi, Russell J. De Souza, Amin Salehi-Abargouei

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Background and Objectives: Vitamin D has received attention for its potential to disrupt cancer processes such as attenuating cell proliferation and exacerbating differentiation and apoptosis. However, whether there exists a role for vitamin D in the treatment of prostate cancer specifically remains controversial. We systematically review the literature to assess whether supplementation with vitamin D influences PSA response and overall survival in patients with prostate cancer. Methods: We searched PubMed, Scopus, ISI Web of Science and Google scholar from inception through up to 10 September 2017 for both before-and-after and randomized trials that evaluated the effect of vitamin D supplementation on the prostate specific antigen (PSA) response rate in participants with prostate cancer. The DerSimonian and Laird, inverse-weighted random-effects model was used to pool effect estimates from the studies. Heterogeneity and potential publication bias were evaluated. Subgroup analyses were also performed. Results: Twenty-two studies (16 before-after and 6 randomized controlled trials) were found and included in meta-analysis. The analysis on controlled clinical trials revealed that PSA change from baseline [weighted mean difference (WMD) = -1.66 ng/ml, 95%CI: -0.69, 0.36, P= 0.543)], PSA response (RR=1.18, 95%CI: 0.97, 1.45, P=0.104) and mortality rate (risk ratio (RR) = 1.05, 95% CI: 0.81-1.36; P=0.713) was not significantly different between vitamin D supplementation and placebo groups. Single arm trials revealed that vitamin D supplementation had had a modest effect on PSA response rate: 19% of those enrolled had at least a 50% reduction in PSA by the end of treatment (95% CI: 7% to 31%; p=0.002). Conclusion: We found that vitamin D modestly increases the PSA response rate in single arm studies. No effect on serum PSA levels, PSA response and mortality was seen in randomized controlled clinical trials. It does not seem patients with prostate cancer benefit from vitamin D supplementation.

Keywords: mortality, prostatic neoplasms, PSA response, vitamin D

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Authors: Jaria A. Polog, Norjana Lao-Pimping, Bedoria M. Macabalang, Monrizah M. Guiling

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Ultrasound-guided single-shot peripheral nerve blocks (PNB) such as erector spinae plane block (ESPB) and pectoral nerve block (PECS I and II) are emerging anesthetic techniques used to provide complete surgical anesthesia without general anesthesia and adequate postoperative analgesia for breast surgeries. Peripheral nerve blocks with sedation could be a better option for breast surgery than general anesthesia in patients with multiple preexisting comorbidities and those refusing general anesthesia. However, an anesthesiologist with optimum knowledge of regional anesthesia and ultrasound experience plays a key factor in the success of doing PNB.

Keywords: mastectomy, peripheral nerve block, erecto spinae block, PECS-2 block

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Authors: Muhammad Solikhudin Nafi, Wahyu Afif Mufida, Mita Erna Wati, Fitri Setyani Rokim, M. Al-Rizqi Dharma Fauzi

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High dose activity without any pre-exercise will impact Delayed Onset Muscle Soreness (DOMS). DOMS known as delayed pain post-exercise and induce skeletal injury which will decrease athletes’ performances. From now on, post-exercise muscle damage can be detected by measuring skeletal troponin I (sTnI) concentration in serum using ELISA but this method needs more time and cost. To prevent decreased athletes performances, screening need to be done rapidly. We want to introduce our new prototype to detect DOMS acutely. Rapid detection tests are based on immunological reaction between skeletal troponin I antibodies and sTnI in human serum or whole blood. Chemical methods that are used in the manufacture of diagnostic test is lateral flow immunoassay. The material used is rat monoclonal antibody sTnI, colloidal gold, anti-mouse IgG, nitrocellulose membrane, conjugate pad, sample pad, wick and backing card. The procedure are made conjugate (colloidal gold and mAb sTnI) and insert into the conjugate pad, gives spray sTnI mAb and anti-mouse IgG into nitrocellulose membrane, and assemble RDT. RDT had been evaluated by measuring the sensitivity of positive human serum (n = 30) and negative human serum (n = 30). Overall sensitivity value was 93% and specificity value was 90%. ADCOR as the first rapid detection test qualitatively showed antigen-antibody reaction and showed good overall performances for screening of muscle damage. Furthermore, these finding still need more improvements to get best results.

Keywords: DOMS, sTnI, rapid detection test, ELISA

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Authors: Sourita Ghosh, Falguni Pati, Suhanya Duraiswamy

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Spheroid, a simple three-dimensional cellular aggregate, allows us to simulate the in-vivo complexity of cellular signaling and interactions in greater detail than traditional 2D cell culture. It can be used as an in-vitro model for drug toxicity testing, tumor modeling and many other such applications specifically for cancer. Our work is focused on the development of an affordable, user-friendly, robust, reproducible, high throughput microfluidic device for water in oil droplet production, which can, in turn, be used for spheroids manufacturing. Here, we have investigated the droplet breakup between two non-Newtonian fluids, viz. silicone oil and decellularized liver matrix, which acts as our extra cellular matrix (ECM) for spheroids formation. We performed some biochemical assays to characterize the liver ECM, as well as rheological studies on our two fluids and observed a critical dependence of capillary number (Ca) on droplet breakup and homogeneous drop formation

Keywords: chip less, droplets, extracellular matrix, liver spheroid

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Authors: Behzad Sinaei, Shahryar Sane, Behzad Kazemi Haki

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Children with different malignancies usually experience potential neurologic complications when treated with radiation therapy, especially if under frequent anesthesia. The aim of this study was to evaluate the neurologic problems associated with anesthesia in pediatrics treated with radiotherapy under anesthesia. The study was a cross-sectional experiment that consisted of 133 pediatric patients with different malignancies who needed anesthesia for performing radiotherapy and were referred to Omid Charity Hospital and Imam Khomeini University Hospital from 2014 to 2020 by the census. P-values less than 0.05 were considered statistically significant (P-value < 0.05). Anesthesia complications in this study were slight and insignificant. Some were due to the effects of the tumor on other important organs or either previous radiation therapy or chemotherapy. For safe anesthesia, considering the effects of tumors on body organs and the neurological complications they cause can greatly help reduce anesthesia complications in pediatrics under radiation therapy.

Keywords: anesthesia, neurologic complications, pediatrics, radiotherapy

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Authors: Mammar Khames, Mustapha Oumouna

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Brucellosis is one of the most common zoonoses in the world. It represents a serious threat to human health; the existence of brucellosis in Algeria dates back to the beginning of the 19th century. Its transmission to humans is through coccobacilli of the genus Brucella following direct contact with contaminated animals or indirectly through the consumption of their unpasteurized dairy products. The present investigation covers a retrospective study on human brucellosis in the district of Medea over a period from 2011 to 2021 at the level of two public health establishments. In the first place, it is at the level of the Directorate of Public Health and in the infectious department level at Medea Hospital, and at the level of the directorate of agricultural services in the third place. The results showed that during these eleven years of study, 795 cases were collected from the department of health and population, and 141 cases were collected from the infectious department of the district of Medea. A total of 56 cases of bovine brucellosis were obtained from the directorate of agricultural services of the district of Medea. Human brucellosis affects all age groups with different percentages, but the rate has been higher in the 20-44 age group, with a predominance of men. However, the geographic distribution map of the cases shows that the western part of the district was the most affected. A cohort of 141 cases was hospitalized at the infectious service level of Medea Hospital. They were 89 men and 52 women. The most common age reached is [20-44] years. The majority were of rural origin. Two serological reactions were performed for diagnosis: the buffered antigen test and Wright's serodiagnosis. Bovine brucellosis affects all age groups with different percentages, but the rate was higher in the 2-to-4-year age group, with a predominance of females. From these data, we conclude that brucellosis has a strong spread in the region studied.

Keywords: human brucellosis, serology, Medea, Algeria

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Authors: Cheng-Cao Sun, Shu-Jun Li, De-Jia Li

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Long non-coding RNA (lncRNA) X inactivate-specific transcript (XIST) has been verified as an oncogenic gene in several human malignant tumors, and its dysregulation was closed associated with tumor initiation, development and progression. Nevertheless, whether the aberrant expression of XIST in human nasopharyngeal carcinoma (NPC) is corrected with malignancy, metastasis or prognosis has not been elaborated. Here, we discovered that XIST was up-regulated in NPC tissues and higher expression of XIST contributed to a markedly poorer survival time. In addition, multivariate analysis demonstrated XIST was an independent risk factor for prognosis. XIST over-expression enhanced, while XIST silencing hampered the cell growth in NPC. Additionally, mechanistic analysis revealed that XIST up-regulated the expression of miR-34a-5p targeted gene E2F3 through acting as a competitive ‘sponge’ of miR-34a-5p. Taking all into account, we concluded that XIST functioned as an oncogene in NPC through up-regulating E2F3 in part through ‘spongeing’ miR-34a-5p.

Keywords: X inactivate-specific transcript; hsa-miRNA-34a-5p, miR-34a-5p; E2F3, nasopharyngeal carcinoma, tumorigenesis

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Authors: Anthony S. Machi, Joseph Minardi

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We present a case report of left atrial myxoma diagnosed by bedside transesophageal (TEE) ultrasound. Left atrial myxoma is the most common benign cardiac tumor and can obstruct blood flow and cause valvular insufficiency. Common symptoms consist of dyspnea, pulmonary edema and other features of left heart failure in addition to thrombus release in the form of tumor fragments. The availability of bedside ultrasound equipment is essential for the quick diagnosis and treatment of various emergency conditions including cardiac neoplasms. A 48-year-old Caucasian female with a four-year history of an untreated renal mass and anemia presented to the ED with two months of sharp, intermittent, bilateral flank pain radiating into the abdomen. She also reported intermittent vomiting and constipation along with generalized body aches, night sweats, and 100-pound weight loss over last year. She had a CT in 2013 showing a 3 cm left renal mass and a second CT in April 2016 showing a 3.8 cm left renal mass along with a past medical history of diverticulosis, chronic bronchitis, dyspnea on exertion, uncontrolled hypertension, and hyperlipidemia. Her maternal family history is positive for breast cancer, hypertension, and Type II Diabetes. Her paternal family history is positive for stroke. She was a current everyday smoker with an 11 pack/year history. Alcohol and drug use were denied. Physical exam was notable for a Grade II/IV systolic murmur at the right upper sternal border, dyspnea on exertion without angina, and a tender left lower quadrant. Her vitals and labs were notable for a blood pressure of 144/96, heart rate of 96 beats per minute, pulse oximetry of 96%, hemoglobin of 7.6 g/dL, hypokalemia, hypochloremia, and multiple other abnormalities. Physicians ordered a CT to evaluate her flank pain which revealed a 7.2 x 8.9 x 10.5 cm mixed cystic/solid mass in the lower pole of the left kidney and a filling defect in the left atrium. Bedside TEE was ordered to follow up on the filling defect. TEE reported an ejection fraction of 60-65% and visualized a mobile 6 x 3 cm mass in the left atrium attached to the interatrial septum extending into the mitral valve. Cardiothoracic Surgery and Urology were consulted and confirmed a diagnosis of left atrial myxoma and clear cell renal cell carcinoma. The patient returned a week later due to worsening nausea and vomiting and underwent emergent nephrectomy, lymph node dissection, and colostomy due to a necrotic colon. Her condition declined over the next four months due to lung and brain metastases, infections, and other complications until she passed away.

Keywords: bedside ultrasound, echocardiography, emergency medicine, left atrial myxoma

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Authors: Shazia Bano

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Nanoconjugates that integrate photo-based therapeutics and diagnostics within a single platform promise great advances in revolutionizing cancer treatments. However, to achieve high therapeutic efficacy, designing functionally efficacious nanocarriers to tightly retain the drug, promoting selective drug localization and release, and the validation of the efficacy of these nanoconjugates is a great challenge. Here we have designed smart multiagent, liposome based targeted photoactivatable multiagent nanoconjugates, doped with a photoactivatable chromophore benzoporphyrin derivative (BPD) labelled with an active targeting ligand cetuximab to target the EGFR receptor (over expressed in various cancer cells) to deliver a combination of therapeutic agents. This study establishes a tunable nanoplatform for the delivery of the photoactivatable multiagent nanoconjugates for tumor-specific accumulation and targeted destruction of cancer cells in complex cancer model to enhance the therapeutic index of the administrated drugs.

Keywords: targeting, photodynamic therapy, photoactivatable, nanoconjugates

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Authors: Abu Salim Mustafa

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Rv3873 is a relatively large size protein (371 amino acids in length) and its gene is located in the immunodominant genomic region of difference (RD)1 that is present in the genome of Mycobacterium tuberculosis but deleted from the genomes of all the vaccine strains of Bacillus Calmette Guerin (BCG) and most other mycobacteria. However, when tested for cellular immune responses using peripheral blood mononuclear cells from tuberculosis patients and BCG-vaccinated healthy subjects, this protein was found to be a major stimulator of cell mediated immune responses in both groups of subjects. In order to further identify the sequence of immunodominant epitopes and explore their Human Leukocyte Antigen (HLA)-restriction for epitope recognition, 24 peptides (25-mers overlapping with the neighboring peptides by 10 residues) covering the sequence of Rv3873 were synthesized chemically using fluorenylmethyloxycarbonyl chemistry and tested in cell mediated immune responses. The results of these experiments helped in the identification of an immunodominant peptide P9 that was recognized by people expressing varying HLA-DR types. Furthermore, it was also predicted to be a promiscuous binder with multiple epitopes for binding to HLA-DR, HLA-DP and HLA-DQ alleles of HLA-class II molecules that present antigens to T helper cells, and to HLA-class I molecules that present antigens to T cytotoxic cells. In addition, the evaluation of peptide P9 using an immunogenicity predictor server yielded a high score (0.94), which indicated a greater probability of this peptide to elicit a protective cellular immune response. In conclusion, P9, a peptide with multiple epitopes and ability to bind several HLA class I and class II molecules for presentation to cells of the cellular immune response, may be useful as a peptide-based vaccine against tuberculosis.

Keywords: mycobacterium tuberculosis, PPE68, peptides, vaccine

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Authors: Hoda Sabry Othman, Randa Helmy Swellem, Galal Abd El-Moein Nawwar

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N-cyanoacetyl glycine is a reactive polyfunctional precursor for synthesis of new difficult accessible compounds including pyridones, thiazolopyridine and others. The key step of this protocol is the formation of different ylidines which underwent Michael addition with carbon nucleophiles affording various heterocyclic compounds. Selected compounds underwent pharmacological evaluation, in vitro against two cell lines; breast cell line (MCF-7),and liver cell line(HEPG2). Compounds 14, 15a and 16 showed IC50 values 8.93, 8.18 and 8.03 (µ/ml) respectively for breast cell line (MCF-7), while the standard drug (Tamoxifen) revealed IC50 8.31. With respect to the liver cell line (HEPG2), compounds 14 and 15a revealed IC50 18.4 and 13.6(µ/ml) respectively while the IC50 of the standard drug(5-Flurouracil) is 25(µ/ml). The antimicrobial activity was also screened and revealed that oxime 7 and ylidine 9f showed a broad-spectrum activity.

Keywords: antitumor, cyanoacetyl glycine, heterocycles, pyridones

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Authors: David J. Foran, Nhan Do, Samuel Ajjarapu, Wenjin Chen, Tahsin Kurc, Joel H. Saltz

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The large-scale data and computational requirements of investigators throughout the clinical and research communities demand an informatics infrastructure that supports both existing and new investigative and translational projects in a robust, secure environment. In some subspecialties of medicine and research, the capacity to generate data has outpaced the methods and technology used to aggregate, organize, access, and reliably retrieve this information. Leading health care centers now recognize the utility of establishing an enterprise-wide, clinical data warehouse. The primary benefits that can be realized through such efforts include cost savings, efficient tracking of outcomes, advanced clinical decision support, improved prognostic accuracy, and more reliable clinical trials matching. The overarching objective of the work presented here is the development and implementation of a flexible Intelligent Retrieval and Interrogation System (IRIS) that exploits the combined use of computational imaging, genomics, and data-mining capabilities to facilitate clinical assessments and translational research in oncology. The proposed System includes a multi-modal, Clinical & Research Data Warehouse (CRDW) that is tightly integrated with a suite of computational and machine-learning tools to provide insight into the underlying tumor characteristics that are not be apparent by human inspection alone. A key distinguishing feature of the System is a configurable Extract, Transform and Load (ETL) interface that enables it to adapt to different clinical and research data environments. This project is motivated by the growing emphasis on establishing Learning Health Systems in which cyclical hypothesis generation and evidence evaluation become integral to improving the quality of patient care. To facilitate iterative prototyping and optimization of the algorithms and workflows for the System, the team has already implemented a fully functional Warehouse that can reliably aggregate information originating from multiple data sources including EHR’s, Clinical Trial Management Systems, Tumor Registries, Biospecimen Repositories, Radiology PAC systems, Digital Pathology archives, Unstructured Clinical Documents, and Next Generation Sequencing services. The System enables physicians to systematically mine and review the molecular, genomic, image-based, and correlated clinical information about patient tumors individually or as part of large cohorts to identify patterns that may influence treatment decisions and outcomes. The CRDW core system has facilitated peer-reviewed publications and funded projects, including an NIH-sponsored collaboration to enhance the cancer registries in Georgia, Kentucky, New Jersey, and New York, with machine-learning based classifications and quantitative pathomics, feature sets. The CRDW has also resulted in a collaboration with the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) at the U.S. Department of Veterans Affairs to develop algorithms and workflows to automate the analysis of lung adenocarcinoma. Those studies showed that combining computational nuclear signatures with traditional WHO criteria through the use of deep convolutional neural networks (CNNs) led to improved discrimination among tumor growth patterns. The team has also leveraged the Warehouse to support studies to investigate the potential of utilizing a combination of genomic and computational imaging signatures to characterize prostate cancer. The results of those studies show that integrating image biomarkers with genomic pathway scores is more strongly correlated with disease recurrence than using standard clinical markers.

Keywords: clinical data warehouse, decision support, data-mining, intelligent databases, machine-learning.

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Authors: Zainab Shaikh, Yusuf Miyanji

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Pilomatrixoma is a benign neoplasm of the hair follicle matrix that is not commonly diagnosed in general practice. This is a case report of a 9-year-old boy who presented with a one-year history of a 19mm x 11 mm swelling in the left infra-orbital region. This was previously undiagnosed in Spain, where the patient resided at the time of initial presentation, due to the language barrier the patient’s family encountered. An ultrasound and magnetic resonance imaging gave useful information regarding surrounding structures for complete tumor excision and indicated that the risk of facial nerve palsy is low. The lesion was surgically excised and a definitive diagnosis was made after histopathology. Pilomatrixoma, although not rare in its occurrence, is rarely this large at the time of excision due to early presentation. This case highlights the importance of including pilomatrixoma in the differential diagnosis of dermal and subcutaneous lesions in the head and neck region, as it is often misdiagnosed due to the lack of awareness of its clinical presentation.

Keywords: pilomatrixoma, swelling, infra-orbital, facial swelling

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Authors: Alhaji Modu Bukar, Faez Firdaus Abdullah Jesse, Che Azurahanim Che Abdullah, Mustapha M. Noordin, Mohd-Lila Mohd Azmia

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Orf virus (ORFV) is the causative agent of a proliferative skin lesion known as contagious ecthyma in sheep and goats. Currently used live attenuated vaccines against ORFV infection have been reported to cause severe outbreaks in vaccinated animals. In this study, we investigated the immunogenicity of the B2L and F1L proteins of the virus, which are thought to elicit a protective immune response The 6-week-old 50 female mice were divided into 8 groups: seven experimental groups and one control group. Each animal in the experimental group received an initial immunisation with the nanoparticles or proteins coated with the nanoparticles, followed by two booster immunizations with the same products 14 days apart. Ten days after the last booster inoculation, the mice were either humanely killed or lethally challenged with UPM /HSN-2-ORFV at a dose of 106 TCID50/mL in a volume of 50 μl. The spleen was examined for histopathological changes and quantification of T cells by flow cytometry. On the other hand, the degree of protection of mice from the lethal virus was evaluated by lesion size, weight loss, and histopathological examination of skin and liver. The results showed that mice immunised with rB2L alone, rB2L-Al₂O₃-NPs, rB2L/rF1L, and rB2L/rF1L-Al₂O₃-NPs elicited statistically higher levels of anti-rB2L and/or rF1L-specific IgA/IgG and CD4/CD8 cell immune responses than mice in the control groups (p < 0.01). The vaccine candidate did not exhibit severe skin damage after monitoring histopathology, morbidity, and mortality. Overall, the results suggest that recombinant rB2L and rF1L antigens may be useful universal vaccine candidates against ORFV infections.

Keywords: orf virus, antigen nanoparticles, virus, nanoparticles

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Authors: Shayli Varasteh Moradi, Wayne A. Johnston, Dejan Gagoski, Kirill Alexandrov

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The demand for a rapid and more efficient technique to identify protein-protein interaction particularly in the areas of therapeutics and diagnostics development is growing. The method described here is a rapid in vitro protein-protein interaction analysis approach based on AlphaLISA technology combined with Leishmania tarentolae cell-free protein production (LTE) system. Cell-free protein synthesis allows the rapid production of recombinant proteins in a multiplexed format. Among available in vitro expression systems, LTE offers several advantages over other eukaryotic cell-free systems. It is based on a fast growing fermentable organism that is inexpensive in cultivation and lysate production. High integrity of proteins produced in this system and the ability to co-express multiple proteins makes it a desirable method for screening protein interactions. Following the translation of protein pairs in LTE system, the physical interaction between proteins of interests is analysed by AlphaLISA assay. The assay is performed using unpurified in vitro translation reaction and therefore can be readily multiplexed. This approach can be used in various research applications such as epitope mapping, antigen-antibody analysis and protein interaction network mapping. The intra-viral protein interaction network of Zika virus was studied using the developed technique. The viral proteins were co-expressed pair-wise in LTE and all possible interactions among viral proteins were tested using AlphaLISA. The assay resulted to the identification of 54 intra-viral protein-protein interactions from which 19 binary interactions were found to be novel. The presented technique provides a powerful tool for rapid analysis of protein-protein interaction with high sensitivity and throughput.

Keywords: AlphaLISA technology, cell-free protein expression, epitope mapping, Leishmania tarentolae, protein-protein interaction

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Authors: A. G. Barua, Uttam Rajkhowa, Pranjal Moni Nath, Nur Abdul Kadir

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Mycobacterium tuberculosis (MTB) is one of the most closely-related intracellular bacterial pathogens, grouped as the M. tuberculosis complex (MTC). MTB, the primary agent of human tuberculosis (TB), can develop clinical TB in animals as 75 percent of canine mycobacterial infection is caused by close contact with an infected human being. In the present study, molecular detection of TB in dogs in three North-eastern states of India, Assam Mizoram, and Nagaland was carried out. So far, there has been a lack of systematic study in these regions, hampered by slow diagnostic methods and poor infrastructure. In an attempt to rectify this situation, molecular epidemiology was carried out for nine months to detect canine TB in a sample of 340 dogs. Isolation of DNA was done with swabs (throat/nasal), nodules of lungs and fluids from 100 suspected dogs and the molecular study were carried out with the help of conventional and real-time PCR. Post-mortem study was also carried out. Our results showed that the prevalence of clinical TB in dogs from a high-risk setting was 1 percent. However, the prevalence of immunological sensitization to M. tuberculosis antigen in dogs living in contact with sputum smeared positive TB cases was almost 50 percent. The latter setting had the maximum impact in terms of TB transmission. During the study period, a survey with a standard questionnaire was carried out in the TB hospitals to study reverse zoonosis. It was observed that an infected human being was one of the major risk factors for dogs to contract the infection. This observation was drawn by examining the probable airborne transmission from humans to their pets or strays. The present study helped to discover the nuances of TB transmission more clearly and systematically as compared to other sporadic tests to detect MTB in canine.

Keywords: Assam and Nagaland, canine TB, India, molecular detection, tuberculosis

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Authors: Shangerganesh Lingeshwaran

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In this presentation, we have performed numerical simulations for a reaction-diffusion equation with various nonlinear density-dependent diffusion operators and proliferation functions. The mathematical model represented by parabolic partial differential equation is considered to study the invasion of gliomas (the most common type of brain tumors) and to describe the growth of cancer cells and response to their treatment. The unknown quantity of the given reaction-diffusion equation is the density of cancer cells and the mathematical model based on the proliferation and migration of glioma cells. A standard Galerkin finite element method is used to perform the numerical simulations of the given model. Finally, important observations on the each of nonlinear diffusion functions and proliferation functions are presented with the help of computational results.

Keywords: glioma invasion, nonlinear diffusion, reaction-diffusion, finite eleament method

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Authors: Mahnaz Zarein, Hamed Shoorei

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Background: Malathion is one of the most toxic agents widely used in agriculture throughout the world. This agent has adverse effects on the functions of multiple organs such as the reproductive system in both male and female genders. On the one hand, daily use of antioxidant supplementations such as hesperidin is capable to neutralize the deleterious impacts of malathion. Therefore, in this experimental study, the protective effects of hesperidin against ovarian toxicity induced by malathion were investigated. Material & Methods: Balb/c adult mice (n=32) were randomly divided into 4 groups including 1) the control group, treated with normal saline, 2) the Mal group, treated with 30mg/kg malathion, daily for 1 month, 3) Mal + Hes group, treated with 20 mg/kg malathion and 20 mg/kg hesperidin, daily for 1 month, and 5) Hes group, treated with 20 mg/kg hesperidin. At the end of the experimental period, mice were anesthetized and their drops of blood were collected to the assessment of some hormones such as LH, FSH, E2, and P4. Also, the right ovaries were used to H&E staining, and the left ovaries were used for IHC staining (PCNA and FSHR). Results: Histopathological assessments showed that the number of follicles, i.e. primordial, primary, and secondary, significantly decreased, while the atretic follicle counts remarkably increased compared to the control group (p<0.05). Hormonal levels revealed that the production of all mentioned hormones decreased in the Mal group in comparison with the control group (p<0.05). The expression of PCNA, as a proliferative marker, and FHSR, as a marker showing maturation, decreased when mice received malathion compared to the control group (p<0.05). Interestingly, treatment with hesperidin significantly neutralized the adverse effects of malathion on all mentioned parameters. Conclusion: Daily use of antioxidant supplementations such as hesperidin could alleviate the ovarian toxicity induced by malathion.

Keywords: malathion, ovary, antioxidant hesperidin, FSHR PCNA, ovary

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Authors: Naomi Seidu, Edward Poluyi, Chibuikem Ikwuegbuenyi, Eghosa Morgan

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The current poor prognosis of glioblastoma has called for the need for an improvement in treatment methods in order to improve its survival rate. Despite the different interventions currently available for this tumor, the average survival is still only a few months. (12-15). The aim is to create a more favorable prognosis and have a reduction in the resistance to treatment currently being experienced, even with surgical interventions and chemotherapy. From the available literature, there is a relationship between the presence of HOX genes (Homeobox genes) and glioblastoma, which could be attributable to the increasing treatment resistance. Hence silencing these genes can be a key to improving survival rates of glioblastoma. A series of studies have highlighted the role that HOX genes play in glioblastoma prognosis. Promotion of human glioblastoma initiation, aggressiveness, and resistance to Temozolomide has been associated with HOXA9. The role of HOX gene expression in cancer stem cells should be studied as it could provide a means of designing CSC-targeted therapies, as CSCs play a part in the initiation and progression of solid tumors.

Keywords: GBM- glioblastoma, HOXA gene- homeobox genes cluster, signaling pathways, temozolomide

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Authors: Cheng-Cao Sun, Shu-Jun Li, De-Jia Li

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Through analysis of a published micro-array-based high-throughput assessment, we discovered that miR-1275 was markedly down-regulated in nasopharyngeal carcinoma (NPC) tissues. However, little is known about its effect and mechanism involved in NPC development and progression. In this study, we investigated the role of miR-1275 on the development of NPC. The results indicated that miR-1275 was significantly down-regulated in primary NPC tissues, and very low levels were found in NPC cell lines. Ectopic expression of miR-1275 in NPC cell lines significantly suppressed cell growth as evidenced by cell viability assay and colony formation assay, through inhibition of HOXB5. In addition, miR-1275 suppresses G1/S transition through inhibition of HOXB5. Further, oncogene HOXB5 was revealed to be a putative target of miR-1275, which was inversely correlated with miR-1275 expression in NPC. Collectively, our study demonstrates that as a tumor suppressor, miR-1275 played a pivotal role on NPC through inhibiting cell proliferation, and suppressing G1/S transition by targeting oncogenic HOXB5.

Keywords: microRNA-1275 (miR-1275), HOXB5, nasopharyngeal carcinoma, proliferation

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Authors: Mohamed El Moctar Abeidi

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The indazole derivatives exhibit a wide spectrum of biological activities. They are known for their anti-tumor, antiplatelet, anti-viral, anti-microbial, anti-inflammatory, anti-leishmania and even anti-spermatogen. As part of our research on the synthesis of a number of heterocycles capable of exhibiting a biological and pharmacological property, due to our ongoing interest in the development of a simple and low-cost procedure for obtaining heterocyclic compounds that may have an interest for medicinal purposes. We present in this work the synthesis of 6-nitro-indazoles derivatives, using two different methods. the first method is the alkylation of Nitroindazole by two different alkylating agents under the conditions of solid/liquid phase transfer catalysis in N, N-dimethylformamide (DMF) in the presence of potassium carbonate (K₂CO₃) as a base, and tetra-n-butylammonium bromide (BTBA) as a catalyst. While the other method is the 1,3-dipolar cycloaddition, in this case, we have undertaken the preparation of bi-heterocyclic containing the 6-nitroindazole associate with group of isoxazoline, isoxazole or 1,2,3-Triazole under normal conditions and, under the catalytic conditions of the click chemistry we were also able to determine the structures without any ambiguity by the ¹H and ¹³C NMR.

Keywords: indazole, 6-nitroindazole, isoxazole, 1, 2, 3-Triazole

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Authors: Khusboo Agrawal, S. Saraf

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Quercetin, a flavonol provides a cellular protection against UV induced oxidative damages due to its excellent free radical scavenging activity and direct pro-apoptopic effect on tumor cells. However, its topical use is limited due to its unfavorable physicochemical properties. The present study was aimed to evaluate the potential of mesoporous silica nanoparticles as topical carrier system for quercetin delivery. Complexes of quercetin with mesoporous silica was prepared with different weight ratios and characterized by thermo gravimetric analysis, X-ray diffraction, high resolution TEM, FT-IR spectroscopy, zeta potential measurements and differential scanning calorimetry The protective effect of this vehicle on UV-induced degradation of the quercetin was investigated revealing a certain positive influence of the inclusion on the photostability over time. Epidermal accumulation and transdermal permeation of this molecule were ex vivo evaluated by using Franz diffusion cells. The immobilization of Quercetin in mesoporous silica nanoparticles (MSNs) increased the stability without undermining the antioxidant efficacy.

Keywords: cancer, MSNs, quercetin, topical delivery

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Authors: Ibrahim M. Labouta, Gina N. Tageldin, Salwa M. Fahmy, Hayam M. Ashour, Mounir A. Khalil, Tamer M. Ibrahim, Nefertiti A. El-Nikhely

Abstract:

Bruton’s tyrosine kinase (BTK) is a critical effector molecule in B cell antigen receptor (BCR) signaling transduction. It regulates B cell proliferation, development and survival. Since BTK is widely expressed in many B cell leukaemias and lymphomas, targeting BTK by small molecules inhibitors became an attractive idea as new treatment modalities for B cell mediated hematologic malignancies. Ibrutinib is the 1st generation BTK inhibitor, approved by FDA for treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). It binds irreversibly to the unique cysteine (Cys481) within the ATP-binding pocket of BTK. Besides ibrutinib, many irreversible covalent BTK inhibitors comprising pyrimidine nucleus such as spebrutinib (phase IIb) showed high selectivity and potency when compared to it. In this study, the designed compounds were based on 5-cyano-2-methylsulfanyl pyrimidine core and decorated with electrophilic warheads which are essential for the optimal activity for targeted covalent inhibition (TCI). However, modifications at pyrimidine C4 or C6 were made by introduction of substituted amines which are provided to behave differently. The synthesized derivatives were evaluated for their anticancer activity in leukemia cell lines (e.g. THP-1). Results showed that, some derivatives exhibited antiproliferative activity with IC50 ranged from 5-50 μM, The in vitro enzymatic inhibitory assay for these compounds against BTK is still under investigation. Nevertheless, we could conclude from the initial biological screening that, the synthesized 4 or 6-subsitituted aminopyrimidines represent promising and novel antileukemic agents. Meanwhile, further studies are still needed to attribute this activity through targeting BTK enzyme and inhibition of BCR signaling pathway.

Keywords: BTK inhibitors, hematologic malignancies, structure based drug design (SBDD), targeted covalent inhibitors (TCI)

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Authors: Paul Lemarignier, Olivier Fiquet, Vincent Pateloup

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In line with the strong desire of nuclear energy players to have ever more effective products in terms of safety, research programs on E-ATF (Enhanced-Accident Tolerant Fuels) that are more resilient, particularly to the loss of coolant, have been launched in all countries with nuclear power plants. Among the multitude of solutions being developed internationally, carcinoembryonic antigen (CEA) and its partners are investigating a promising solution, which is the realization of CERMET (CERamic-METal) type fuel pellets made of a matrix of fissile material, uranium dioxide UO2, which has a low thermal conductivity, and a metallic phase with a high thermal conductivity to improve heat evacuation. Work has focused on the development by powder metallurgy of micro-structured CERMETs, characterized by networks of metallic phase embedded in the UO₂ matrix. Other types of macro-structured CERMETs, based on concepts proposed by thermal simulation studies, have been developed with a metallic phase with a specific geometry to optimize heat evacuation. This solution could not be developed using traditional processes, so additive manufacturing, which revolutionizes traditional design principles, is used to produce these innovative prototype concepts. At CEA Cadarache, work is first carried out on a non-radioactive surrogate material, alumina, in order to acquire skills and to develop the equipment, in particular the robocasting machine, an additive manufacturing technique selected for its simplicity and the possibility of optimizing the paste formulations. A manufacturing chain was set up, with the pastes production, the 3D printing of pellets, and the associated thermal post-treatment. The work leading to the first elaborations of macro-structured alumina/molybdenum CERMETs will be presented. This work was carried out with the support of Framatome and EdF.

Keywords: additive manufacturing, alumina, CERMET, molybdenum, nuclear safety

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Authors: Dmitry Nosik, Nickolay Nosik, Elli Kaplina, Olga Lobach, Marina Chataeva, Lev Rasnetsov

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Background and aims: Human Immunodeficiency Virus (HIV) infection is very often associated with Herpes Simplex Virus (HSV) infection but HIV patients are treated with a cocktail of antiretroviral drugs which are toxic. The use of an antiviral drug which will be active against both viruses like ferrovir found in our previous studies is rather actual. Earlier we had shown that Fullerene poly-amino capronic acid (FPACA) was active in case of monoinfection of HIV-1 or HSV-1. The aim of the study was to analyze the efficiency of FPACA against mixed infection of HIV and HSV. Methods: The peripheral blood lymphocytes, CEM, MT-4 cells were simultaneously infected with HIV-1 and HSV-1. FPACA was added 1 hour before infection. Cells viability was detected by MTT assay, virus antigens detected by ELISA, syncytium formation detected by microscopy. The different multiplicity of HIV-1/HSV-1 ratio was used. Results: The double viral HIV-1/HSV-1 infection was more cytopathic comparing with monoinfections. In mixed infection by the HIV-1/HSV-1 concentration of HIV-1 antigens and syncytium formations increased by 1,7 to 2,3 times in different cells in comparison with the culture infected with HIV-1 alone. The concentration of HSV-1 increased by 1,5-1,7 times, respectively. Administration of FPACA (1 microg/ml) protected cells: HIV-1/HSV-1 (1:1) – 80,1%; HIV-1/HSV-1 (1:4) – 57,2%; HIV-1/HSV-1 (1:8) – 46,3 %; HIV-1/HSV-1 (1:16) – 17,0%. Virus’s antigen levels were also reduced. Syncytium formation was totally inhibited in all cases of mixed infection. Conclusion: FPACA showed antiviral activity in case of mixed viral infection induced by Human Immunodeficiency Virus and Herpes Simplex Virus. The effect of viral inhibition increased with the multiplicity of HIV-1 in the inoculum. The mechanism of FPACA action is connected with the blocking of the virus particles adsorption to the cells and it could be suggested that it can have an antiviral activity against some other viruses too. Now FPACA could be considered as a potential drug for treatment of HIV disease complicated with opportunistic herpes viral infection.

Keywords: antiviral drug, human immunodeficiency virus (hiv), herpes simplex virus (hsv), mixed viral infection

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Authors: Sina Mahdavi, Mahdi Asghari Ozma

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Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human Varicella-zoster virus (VZV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on VZV retrovirus infection in MS disease progression. For this study, the keywords "Multiple sclerosis", " Human Varicella-zoster virus ", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched and 14 articles were chosen, studied, and analyzed. Analysis of the amino acid sequences of HNRNPA1 with VZV proteins has shown a 62% amino acid sequence similarity between VZV gE and the PrLD/M9 epitope region (TNPO1 binding domain) of mutant HNRNPA1. A heterogeneous nuclear ribonucleoprotein (hnRNP), which is produced by HNRNPA1, is involved in the processing and transfer of mRNA and pre-mRNA. Mutant HNRNPA1 mimics gE of VZV as an antigen that leads to autoantibody production. Mutant HnRNPA1 translocates to the cytoplasm, after aggregation is presented by MHC class I, followed by CD8 + cells. Of these, antibodies and immune cells against the gE epitopes of VZV remain due to the memory immune response, causing neurodegeneration and the development of MS in genetically predisposed individuals. VZV expression during the course of MS is present in genetically predisposed individuals with HNRNPA1 mutation, suggesting a link between VZV and MS, and that this virus may play a role in the development of MS by inducing an inflammatory state. Therefore, measures to modulate VZV expression may be effective in reducing inflammatory processes in demyelinated areas of MS patients in genetically predisposed individuals.

Keywords: multiple sclerosis, varicella-zoster virus, central nervous system, autoimmunity

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Authors: Monika Malik, Pooja Arora, Ruchi Sachdeva, Vishnampettai G. Ramachandran, Rahul Pal

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Apoptotic debris is believed to be the antigenic trigger in lupus. Whether such debris and autoantibodies induced in lupus-prone mice which specifically recognize its constituents can mediate differential effects on innate and humoral responses in such mice was assessed. The influence of apoptotic blebs and apoptotic cell-reactive monoclonal antibodies on phenotypic markers expressed on bone marrow-derived dendritic cells (BMDCs) and secreted cytokines were evaluated. Sera from lupus-prone and healthy mice immunized with the antibodies were analyzed for anti-self reactivity. Apoptotic blebs, as well as somatically-mutated IgG and non-mutated IgM apoptotic-cell reactive monoclonal antibodies, induced the preferential maturation of BMDCs derived from lupus-prone mice relative to BMDCs derived from healthy mice; antibody specificity and cell genotype both influenced the secretion of inflammatory cytokines. Immunization of lupus-prone mice with IgM and IgG antibodies led to hypergammaglobulinemia; elicited antibodies were self-reactive, and exhibited enhanced recognition of lupus-associated autoantigens (dsDNA, Ro60, RNP68, and Sm) in comparison with adjuvant-induced sera. While ‘natural’ IgM antibodies are believed to contribute to immune homeostasis, this study reveals that apoptotic cell-reactive IgM antibodies can promote inflammation and drive anti-self responses in lupus. Only in lupus-prone mice did immunization with IgG auto-antibodies enhance the kinetics of humoral anti-self responses, resulting in advanced-onset glomerulosclerosis. This study reveals that preferential innate and humoral recognition of the products of cell death in an autoimmune milieu influences the indices associated with lupus pathology.

Keywords: antigen spreading, apoptotic cell-reactive pathogenic IgG, and IgM autoantibodies, glomerulosclerosis, lupus

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Authors: Amir Ghasemlouei, Alireza Khalaj

Abstract:

In women, cancer of the breast is one of the most common incident cancer and cause of death from cancer .we reviewed the prevalence of obesity and its association with breast cancer. In this study, a total of 25 articles regarding the subject matter of the article have been presented in which 640 patients were examined that 320 patients with breast cancer and 320 were controls. The distribution of breast cancer patients and controls with respect to their anthropometric indices in patients with higher weight, which was statistically significant (60.2 ± 10.2 kg) compared with control group (56.1 ± 11.3 kg). The body mass index of patients was (26.06+/-3.42) and significantly higher than the control group (24.1+/-1.7). Obesity leads to increased levels of adipose tissue in the body that can be stored toxins and carcinogens to produce a continuous supply. Due to the high level of fat and the role of estrogen in a woman is endogenous estrogen of the tumor and regulate the activities of growth steroids, obesity is a risk factor for breast cancer is confirmed. Our study and other studies show that obesity is a risk factor for breast cancer. And with a weight loss intervention for breast cancer can be prevented in the future.

Keywords: breast cancer, review study, obesity, overweight

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