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gene</title> <meta name="description" content="Search results for: Calmodulin gene"> <meta name="keywords" content="Calmodulin gene"> <meta name="viewport" content="width=device-width, initial-scale=1, minimum-scale=1, maximum-scale=1, user-scalable=no"> <meta charset="utf-8"> <link href="https://cdn.waset.org/favicon.ico" type="image/x-icon" rel="shortcut icon"> <link href="https://cdn.waset.org/static/plugins/bootstrap-4.2.1/css/bootstrap.min.css" rel="stylesheet"> <link href="https://cdn.waset.org/static/plugins/fontawesome/css/all.min.css" rel="stylesheet"> <link href="https://cdn.waset.org/static/css/site.css?v=150220211555" rel="stylesheet"> </head> <body> <header> <div class="container"> <nav class="navbar navbar-expand-lg navbar-light"> <a class="navbar-brand" href="https://waset.org"> <img src="https://cdn.waset.org/static/images/wasetc.png" alt="Open Science Research Excellence" title="Open Science Research Excellence" /> </a> <button class="d-block d-lg-none navbar-toggler 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id="custom-search-input"> <div class="input-group"> <i class="fas fa-search"></i> <input type="text" class="search-query" name="q" placeholder="Author, Title, Abstract, Keywords" value="Calmodulin gene"> <input type="submit" class="btn_search" value="Search"> </div> </div> </form> </div> </div> <div class="row mt-3"> <div class="col-sm-3"> <div class="card"> <div class="card-body"><strong>Commenced</strong> in January 2007</div> </div> </div> <div class="col-sm-3"> <div class="card"> <div class="card-body"><strong>Frequency:</strong> Monthly</div> </div> </div> <div class="col-sm-3"> <div class="card"> <div class="card-body"><strong>Edition:</strong> International</div> </div> </div> <div class="col-sm-3"> <div class="card"> <div class="card-body"><strong>Paper Count:</strong> 1519</div> </div> </div> </div> <h1 class="mt-3 mb-3 text-center" style="font-size:1.6rem;">Search results for: Calmodulin gene</h1> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">19</span> Clinico-pathological Study of Xeroderma Pigmentosa: A Case Series of Eight Cases</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Kakali%20Roy">Kakali Roy</a>, <a href="https://publications.waset.org/abstracts/search?q=Sahana%20P.%20Raju"> Sahana P. Raju</a>, <a href="https://publications.waset.org/abstracts/search?q=Subhra%20Dhar"> Subhra Dhar</a>, <a href="https://publications.waset.org/abstracts/search?q=Sandipan%20Dhar"> Sandipan Dhar</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Introduction: Xeroderma pigmentosa (XP) is a rare inherited (autosomal recessive) disease resulting from impairment in DNA repair that involves recognition and repair of ultraviolet radiation (UVR) induced DNA damage in the nucleotide excision repair pathway. Which results in increased photosensitivity, UVR induced damage to skin and eye, increased susceptibility of skin and ocular cancer, and progressive neurodegeneration in some patients. XP is present worldwide, with higher incidence in areas having frequent consanguinity. Being extremely rare, there is limited literature on XP and associated complications. Here, the clinico-pathological experience (spectrum of clinical presentation, histopathological findings of malignant skin lesions, and progression) of managing 8 cases of XP is presented. Methodology: A retrospective study was conducted in a pediatric tertiary care hospital in eastern India during a ten-year period from 2013 to 2022. A clinical diagnosis was made based on severe sun burn or premature photo-aging and/or onset of cutaneous malignancies at early age (1st decade) in background of consanguinity and autosomal recessive inheritance pattern in family. Results: The mean age of presentation was 1.2 years (range of 7month-3years), while three children presented during their infancy. Male to female ratio was 5:3, and all were born of consanguineous marriage. They presented with dermatological manifestations (100%) followed by ophthalmic (75%) and/or neurological symptoms (25%). Patients had normal skin at birth but soon developed extreme sensitivity to UVR in the form of exaggerated sun tanning, burning, and blistering on minimal sun exposure, followed by abnormal skin pigmentation like freckles and lentiginosis. Subsequently, over time there was progressive xerosis, atrophy, wrinkling, and poikiloderma. Six patients had varied degree of ocular involvement, while three of them had severe manifestation, including madarosis, tylosis, ectropion, Lagopthalmos, Pthysis bulbi, clouding and scarring of the cornea with complete or partial loss of vision, and ophthalmic malignancies. 50% (n=4) cases had skin and ocular pre-malignant (actinic keratosis) and malignant lesions, including melanoma and non melanoma skin cancer (NMSC) like squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in their early childhood. One patient had simultaneous occurrence of multiple malignancies together (SCC, BCC, and melanoma). Subnormal intelligence was noticed as neurological feature, and none had sensory neural hearing loss, microcephaly, neuroregression, or neurdeficit. All the patients had been being managed by a multidisciplinary team of pediatricians, dermatologists, ophthalmologists, neurologists and psychiatrists. Conclusion: Although till date there is no complete cure for XP and the disease is ultimately fatal. But increased awareness, early diagnosis followed by persistent vigorous protection from UVR, and regular screening for early detection of malignancies along with psychological support can drastically improve patients’ quality of life and life expectancy. Further research is required on formulating optimal management of XP, specifically the role and possibilities of gene therapy in XP. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=childhood%20malignancies" title="childhood malignancies">childhood malignancies</a>, <a href="https://publications.waset.org/abstracts/search?q=dermato-pathological%20findings" title=" dermato-pathological findings"> dermato-pathological findings</a>, <a href="https://publications.waset.org/abstracts/search?q=eastern%20India" title=" eastern India"> eastern India</a>, <a href="https://publications.waset.org/abstracts/search?q=Xeroderma%20pigmentosa" title=" Xeroderma pigmentosa"> Xeroderma pigmentosa</a> </p> <a href="https://publications.waset.org/abstracts/162111/clinico-pathological-study-of-xeroderma-pigmentosa-a-case-series-of-eight-cases" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/162111.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">76</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">18</span> Targeting TACI Signaling Enhances Immune Function and Halts Chronic Lymphocytic Leukemia Progression</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Yong%20H%20Sheng">Yong H Sheng</a>, <a href="https://publications.waset.org/abstracts/search?q=Beatriz%20Garcill%C3%A1n"> Beatriz Garcillán</a>, <a href="https://publications.waset.org/abstracts/search?q=Eden%20Whitlock"> Eden Whitlock</a>, <a href="https://publications.waset.org/abstracts/search?q=Yukli%20Freedman"> Yukli Freedman</a>, <a href="https://publications.waset.org/abstracts/search?q=SiLing%20Yang"> SiLing Yang</a>, <a href="https://publications.waset.org/abstracts/search?q=M%20Arifur%20Rahman"> M Arifur Rahman</a>, <a href="https://publications.waset.org/abstracts/search?q=Nicholas%20Weber"> Nicholas Weber</a>, <a href="https://publications.waset.org/abstracts/search?q=Fabienne%20Mackay"> Fabienne Mackay</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Chronic lymphocytic leukemia (CLL) is closely associated with immune dysfunction, yet the mechanisms underlying this immune deficiency remain poorly understood. Transmembrane Activator and CAML Interactor (TACI), a receptor known for its role in IL-10 regulation and autoimmunity, to the best of our knowledge has not been investigated in the context of anti-tumor immunity or its impact on CLL progression. This study addresses the gap by exploring the role of TACI in regulating CLL cells within the tumor microenvironment and its broader effects on disease progression and immune competence. We utilized the Eµ-TCL1 mouse model to generate CLL mice deficient in TACI and examined the consequences of TACI loss in adoptive transfer models over a five-week period. Comprehensive transcriptomic analysis, including RNA sequencing and microarray, was employed to determine TACI’s influence on the CLL gene expression profile. Additionally, we studied TACI’s direct role in CLL cell migration and immune modulation using patient-derived CLL cells in culture and Patient-Derived Xenograph (PDX) models. Our findings demonstrate that TACI signaling plays a pivotal role in promoting CLL progression and immune suppression. Loss of TACI signaling significantly inhibited CLL development and enhanced immune functionality. When TACI+/+ or TACI-/- TCL1 CLL cells were transferred into wild-type recipient mice, those receiving TACI-deficient cells showed reduced disease progression and lower incidence of CLL. Mice with TACI-/- CLL cells exhibited normalized serum levels of pro-inflammatory cytokines IL-6 and IL-10, restored proportions of T-cell subsets, and improved immune compartment function compared to counterparts with TACI+/+ CLL cells. Mechanistically, TACI-deficient CLL cells expressed significantly lower levels of IL-10, TNF, and inhibitory receptors such as PD-L1 and PD-L2. These cells also display restored circulating immunoglobulin levels and responses to T cell-dependent antigens, highlighting a recovery of immune competence. Further mechanistic studies revealed that TACI signaling drives CLL cell migration and homing to the spleen, where these cells actively establish an immunosuppressive microenvironment that supports immune evasion and tumor growth. Patient-derived CLL cells and PDX models confirmed TACI’s direct role in enhancing CLL cell migration and fostering immune suppression, emphasizing its critical function in the tumor microenvironment. By disrupting TACI signaling, we observed a reduction in CLL-associated immune suppression and tumor progression, offering a promising therapeutic avenue. This study establishes, for the first time, that targeting TACI disrupts key mechanisms underlying CLL progression while preserving vital immune functions. Unlike existing treatments that often impair immunity and lead to infection-related complications, TACI inhibition offers the dual benefit of controlling disease and maintaining immune homeostasis. These findings provide a strong rationale for developing therapeutic strategies that inhibit TACI as a means to improve outcomes in CLL patients. Beyond its implications for CLL, this research underscores the broader importance of TACI in regulating immune-tumor interactions, paving the way for future studies into its role in other malignancies. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=chronic%20lymphocytic%20leukemia" title="chronic lymphocytic leukemia">chronic lymphocytic leukemia</a>, <a href="https://publications.waset.org/abstracts/search?q=TACI" title=" TACI"> TACI</a>, <a href="https://publications.waset.org/abstracts/search?q=IL-10" title=" IL-10"> IL-10</a>, <a href="https://publications.waset.org/abstracts/search?q=immune%20suppression" title=" immune suppression"> immune suppression</a> </p> <a href="https://publications.waset.org/abstracts/195108/targeting-taci-signaling-enhances-immune-function-and-halts-chronic-lymphocytic-leukemia-progression" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/195108.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">7</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">17</span> Photosynthesis Metabolism Affects Yield Potentials in Jatropha curcas L.: A Transcriptomic and Physiological Data Analysis</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Nisha%20Govender">Nisha Govender</a>, <a href="https://publications.waset.org/abstracts/search?q=Siju%20Senan"> Siju Senan</a>, <a href="https://publications.waset.org/abstracts/search?q=Zeti-Azura%20Hussein"> Zeti-Azura Hussein</a>, <a href="https://publications.waset.org/abstracts/search?q=Wickneswari%20Ratnam"> Wickneswari Ratnam</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Jatropha curcas, a well-described bioenergy crop has been extensively accepted as future fuel need especially in tropical regions. Ideal planting material required for large-scale plantation is still lacking. Breeding programmes for improved J. curcas varieties are rendered difficult due to limitations in genetic diversity. Using a combined transcriptome and physiological data, we investigated the molecular and physiological differences in high and low yielding Jatropha curcas to address plausible heritable variations underpinning these differences, in regard to photosynthesis, a key metabolism affecting yield potentials. A total of 6 individual Jatropha plant from 4 accessions described as high and low yielding planting materials were selected from the Experimental Plot A, Universiti Kebangsaan Malaysia (UKM), Bangi. The inflorescence and shoots were collected for transcriptome study. For the physiological study, each individual plant (n=10) from the high and low yielding populations were screened for agronomic traits, chlorophyll content and stomatal patterning. The J. curcas transcriptomes are available under BioProject PRJNA338924 and BioSample SAMN05827448-65, respectively Each transcriptome was subjected to functional annotation analysis of sequence datasets using the BLAST2Go suite; BLASTing, mapping, annotation, statistical analysis and visualization Large-scale phenotyping of the number of fruits per plant (NFPP) and fruits per inflorescence (FPI) classified the high yielding Jatropha accessions with average NFPP =60 and FPI > 10, whereas the low yielding accessions yielded an average NFPP=10 and FPI < 5. Next generation sequencing revealed genes with differential expressions in the high yielding Jatropha relative to the low yielding plants. Distinct differences were observed in transcript level associated to photosynthesis metabolism. DEGs collection in the low yielding population showed comparable CAM photosynthetic metabolism and photorespiration, evident as followings: phosphoenolpyruvate phosphate translocator chloroplastic like isoform with 2.5 fold change (FC) and malate dehydrogenase (2.03 FC). Green leaves have the most pronounced photosynthetic activity in a plant body due to significant accumulation of chloroplast. In most plants, the leaf is always the dominant photosynthesizing heart of the plant body. Large number of the DEGS in the high-yielding population were found attributable to chloroplast and chloroplast associated events; STAY-GREEN chloroplastic, Chlorophyllase-1-like (5.08 FC), beta-amylase (3.66 FC), chlorophyllase-chloroplastic-like (3.1 FC), thiamine thiazole chloroplastic like (2.8 FC), 1-4, alpha glucan branching enzyme chloroplastic amyliplastic (2.6FC), photosynthetic NDH subunit (2.1 FC) and protochlorophyllide chloroplastic (2 FC). The results were parallel to a significant increase in chlorophyll a content in the high yielding population. In addition to the chloroplast associated transcript abundance, the TOO MANY MOUTHS (TMM) at 2.9 FC, which code for distant stomatal distribution and patterning in the high-yielding population may explain high concentration of CO2. The results were in agreement with the role of TMM. Clustered stomata causes back diffusion in the presence of gaps localized closely to one another. We conclude that high yielding Jatropha population corresponds to a collective function of C3 metabolism with a low degree of CAM photosynthetic fixation. From the physiological descriptions, high chlorophyll a content and even distribution of stomata in the leaf contribute to better photosynthetic efficiency in the high yielding Jatropha compared to the low yielding population. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=chlorophyll" title="chlorophyll">chlorophyll</a>, <a href="https://publications.waset.org/abstracts/search?q=gene%20expression" title=" gene expression"> gene expression</a>, <a href="https://publications.waset.org/abstracts/search?q=genetic%20variation" title=" genetic variation"> genetic variation</a>, <a href="https://publications.waset.org/abstracts/search?q=stomata" title=" stomata"> stomata</a> </p> <a href="https://publications.waset.org/abstracts/67246/photosynthesis-metabolism-affects-yield-potentials-in-jatropha-curcas-l-a-transcriptomic-and-physiological-data-analysis" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/67246.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">239</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">16</span> Targeting Matrix Metalloprotease-9 to Reduce Coronary Artery Manifestations of Kawasaki’s Disease</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Mohammadjavad%20Sotoudeheian">Mohammadjavad Sotoudeheian</a>, <a href="https://publications.waset.org/abstracts/search?q=Navid%20Farahmandian"> Navid Farahmandian</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Kawasaki disease (KD) is the primary cause of acquired pediatric heart disease as an acute vasculitis. In children with prolonged fever, rash, and inflammation of the mucosa KD must be considered as a clinical diagnosis. There is a persuasive suggestion of immune-mediated damage as the pathophysiologic cascade of KD. For example, the invasion of cytotoxic T-cells supports a viral etiology and the inflammasome of the innate immune system is a critical component in the vasculitis formation in KD. Animal models of KD propose the cytokine profiles, such as increased IL-1 and GM-CSF, which cause vascular damage. CRP and IFN-γ elevated expression and the upregulation of IL-6, and IL-10 production are also described in previous studies. Untreated KD is a critical risk factor for coronary artery diseases and myocardial infarction. Vascular damage may encompass amplified T-cell activity. SMAD3 is an essential molecule in down-regulating T-cells and increasing expression of FoxP3. It has a critical effect in the differentiation of regulatory T-cells. The discrepancy of regulatory T-cells and pro-inflammatory Th17 has been studied in acute coronary syndrome during KD. However in the coronary artery damaged lymphocytes and IgA plasma cells are seen at the lesion locations, the major immune cells in the coronary lesions are monocytes/macrophages and neutrophils. These cells secrete TNF-α, and activates matrix metalloprotease (MMP)-9, reducing the integrity of vessels and prompting patients to arise aneurysm. MMPs can break down the components of the extracellular matrix and assist immune cell movement. IVIG as an effective form of treatment clarified the role of the immune system, which may target pathogenic antigens and regulate cytokine production. Several reports have revealed that in the coronary arteries, high expression of MMP-9 in monocyte/macrophage results in pathologic cascades. Curcumin is a potent antioxidant and anti-inflammatory molecule. Curcumin decreases the production of reactive oxygen and nitrogen species and inhibits transcription factors like AP-1 and NF-κB. Curcumin also contains the characteristics of inhibitory effects on MMPs, especially MMP-9. The upregulation of MMP-9 is an important cellular response. Curcumin treatment caused a reverse effect and down-regulates MMP-9 gene expression which may fund the anti-inflammatory effect. Curcumin inhibits MMP-9 expression via PKC and AMPK-dependent pathways in Human monocytes cells. Elevated expression and activity of MMP-9 are correlated with advanced vascular lesions. AMPK controls lipid metabolism and oxidation, and protein synthesis. AMPK is also necessary for the MMP-9 activity and THP-1 cell adhesion to endothelial cells. Curcumin was shown to inhibit the activation of AMPKα. Compound C (AMPK inhibitor) inhibits MMP-9 expression level. Therefore, through inactivating AMPKs and PKC, curcumin decreases the MMP-9 level, which results in inhibiting monocyte/macrophage differentiation. Compound C also suppress the phosphorylation of three major classes of MAP kinase signaling, suggesting that curcumin may suppress MMP-9 level by inactivation of MAPK pathways. MAPK cascades are activated to induce the expression of MMP-9. Curcumin inhibits MAPKs phosphorylation, which contributes to the down-regulation of MMP-9. This study demonstrated that the potential inhibitory properties of curcumin over MMP-9 lead to a therapeutic strategy to reduce the risk of coronary artery involvement during KD. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=MMP-9" title="MMP-9">MMP-9</a>, <a href="https://publications.waset.org/abstracts/search?q=coronary%20artery%20aneurysm" title=" coronary artery aneurysm"> coronary artery aneurysm</a>, <a href="https://publications.waset.org/abstracts/search?q=Kawasaki%E2%80%99s%20disease" title=" Kawasaki’s disease"> Kawasaki’s disease</a>, <a href="https://publications.waset.org/abstracts/search?q=curcumin" title=" curcumin"> curcumin</a>, <a href="https://publications.waset.org/abstracts/search?q=AMPK" title=" AMPK"> AMPK</a>, <a href="https://publications.waset.org/abstracts/search?q=immune%20system" title=" immune system"> immune system</a>, <a href="https://publications.waset.org/abstracts/search?q=NF-%CE%BAB" title=" NF-κB"> NF-κB</a>, <a href="https://publications.waset.org/abstracts/search?q=MAPK" title=" MAPK"> MAPK</a> </p> <a href="https://publications.waset.org/abstracts/151199/targeting-matrix-metalloprotease-9-to-reduce-coronary-artery-manifestations-of-kawasakis-disease" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/151199.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">304</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">15</span> CLOUD Japan: Prospective Multi-Hospital Study to Determine the Population-Based Incidence of Hospitalized Clostridium difficile Infections</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Kazuhiro%20Tateda">Kazuhiro Tateda</a>, <a href="https://publications.waset.org/abstracts/search?q=Elisa%20Gonzalez"> Elisa Gonzalez</a>, <a href="https://publications.waset.org/abstracts/search?q=Shuhei%20Ito"> Shuhei Ito</a>, <a href="https://publications.waset.org/abstracts/search?q=Kirstin%20Heinrich"> Kirstin Heinrich</a>, <a href="https://publications.waset.org/abstracts/search?q=Kevin%20Sweetland"> Kevin Sweetland</a>, <a href="https://publications.waset.org/abstracts/search?q=Pingping%20Zhang"> Pingping Zhang</a>, <a href="https://publications.waset.org/abstracts/search?q=Catia%20Ferreira"> Catia Ferreira</a>, <a href="https://publications.waset.org/abstracts/search?q=Michael%20Pride"> Michael Pride</a>, <a href="https://publications.waset.org/abstracts/search?q=Jennifer%20Moisi"> Jennifer Moisi</a>, <a href="https://publications.waset.org/abstracts/search?q=Sharon%20Gray"> Sharon Gray</a>, <a href="https://publications.waset.org/abstracts/search?q=Bennett%20Lee"> Bennett Lee</a>, <a href="https://publications.waset.org/abstracts/search?q=Fred%20Angulo"> Fred Angulo</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Clostridium difficile (C. difficile) is the most common cause of antibiotic-associated diarrhea and infectious diarrhea in healthcare settings. Japan has an aging population; the elderly are at increased risk of hospitalization, antibiotic use, and C. difficile infection (CDI). Little is known about the population-based incidence and disease burden of CDI in Japan although limited hospital-based studies have reported a lower incidence than the United States. To understand CDI disease burden in Japan, CLOUD (Clostridium difficile Infection Burden of Disease in Adults in Japan) was developed. CLOUD will derive population-based incidence estimates of the number of CDI cases per 100,000 population per year in Ota-ku (population 723,341), one of the districts in Tokyo, Japan. CLOUD will include approximately 14 of the 28 Ota-ku hospitals including Toho University Hospital, which is a 1,000 bed tertiary care teaching hospital. During the 12-month patient enrollment period, which is scheduled to begin in November 2018, Ota-ku residents > 50 years of age who are hospitalized at a participating hospital with diarrhea ( > 3 unformed stools (Bristol Stool Chart 5-7) in 24 hours) will be actively ascertained, consented, and enrolled by study surveillance staff. A stool specimen will be collected from enrolled patients and tested at a local reference laboratory (LSI Medience, Tokyo) using QUIK CHEK COMPLETE® (Abbott Laboratories). which simultaneously tests specimens for the presence of glutamate dehydrogenase (GDH) and C. difficile toxins A and B. A frozen stool specimen will also be sent to the Pfizer Laboratory (Pearl River, United States) for analysis using a two-step diagnostic testing algorithm that is based on detection of C. difficile strains/spores harboring toxin B gene by PCR followed by detection of free toxins (A and B) using a proprietary cell cytotoxicity neutralization assay (CCNA) developed by Pfizer. Positive specimens will be anaerobically cultured, and C. difficile isolates will be characterized by ribotyping and whole genomic sequencing. CDI patients enrolled in CLOUD will be contacted weekly for 90 days following diarrhea onset to describe clinical outcomes including recurrence, reinfection, and mortality, and patient reported economic, clinical and humanistic outcomes (e.g., health-related quality of life, worsening of comorbidities, and patient and caregiver work absenteeism). Studies will also be undertaken to fully characterize the catchment area to enable population-based estimates. The 12-month active ascertainment of CDI cases among hospitalized Ota-ku residents with diarrhea in CLOUD, and the characterization of the Ota-ku catchment area, including estimation of the proportion of all hospitalizations of Ota-ku residents that occur in the CLOUD-participating hospitals, will yield CDI population-based incidence estimates, which can be stratified by age groups, risk groups, and source (hospital-acquired or community-acquired). These incidence estimates will be extrapolated, following age standardization using national census data, to yield CDI disease burden estimates for Japan. CLOUD also serves as a model for studies in other countries that can use the CLOUD protocol to estimate CDI disease burden. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=Clostridium%20difficile" title="Clostridium difficile">Clostridium difficile</a>, <a href="https://publications.waset.org/abstracts/search?q=disease%20burden" title=" disease burden"> disease burden</a>, <a href="https://publications.waset.org/abstracts/search?q=epidemiology" title=" epidemiology"> epidemiology</a>, <a href="https://publications.waset.org/abstracts/search?q=study%20protocol" title=" study protocol"> study protocol</a> </p> <a href="https://publications.waset.org/abstracts/99749/cloud-japan-prospective-multi-hospital-study-to-determine-the-population-based-incidence-of-hospitalized-clostridium-difficile-infections" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/99749.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">261</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">14</span> Phenotype and Psychometric Characterization of Phelan-Mcdermid Syndrome Patients</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=C.%20Bel">C. Bel</a>, <a href="https://publications.waset.org/abstracts/search?q=J.%20Nevado"> J. Nevado</a>, <a href="https://publications.waset.org/abstracts/search?q=F.%20Ciceri"> F. Ciceri</a>, <a href="https://publications.waset.org/abstracts/search?q=M.%20Ropacki"> M. Ropacki</a>, <a href="https://publications.waset.org/abstracts/search?q=T.%20Hoffmann"> T. Hoffmann</a>, <a href="https://publications.waset.org/abstracts/search?q=P.%20Lapunzina"> P. Lapunzina</a>, <a href="https://publications.waset.org/abstracts/search?q=C.%20Buesa"> C. Buesa</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Background: The Phelan-McDermid syndrome (PMS) is a genetic disorder caused by the deletion of the terminal region of chromosome 22 or mutation of the SHANK3 gene. Shank3 disruption in mice leads to dysfunction of synaptic transmission, which can be restored by epigenetic regulation with both Lysine Specific Demethylase 1 (LSD1) inhibitors. PMS subjects result in a variable degree of intellectual disability, delay or absence of speech, autistic spectrum disorders symptoms, low muscle tone, motor delays and epilepsy. Vafidemstat is an LSD1 inhibitor in Phase II clinical development with a well-established and favorable safety profile, and data supporting the restoration of memory and cognition defects as well as reduction of agitation and aggression in several animal models and clinical studies. Therefore, vafidemstat has the potential to become a first-in-class precision medicine approach to treat PMS patients. Aims: The goal of this research is to perform an observational trial to psychometrically characterize individuals carrying deletions in SHANK3 and build a foundation for subsequent precision psychiatry clinical trials with vafidemstat. Methodology: This study is characterizing the clinical profile of 20 to 40 subjects, > 16-year-old, with genotypically confirmed PMS diagnosis. Subjects will complete a battery of neuropsychological scales, including the Repetitive Behavior Questionnaire (RBQ), Vineland Adaptive Behavior Scales, Escala de Observación para el Diagnostico del Autismo (Autism Diagnostic Observational Scale) (ADOS)-2, the Battelle Developmental Inventory and the Behavior Problems Inventory (BPI). Results: By March 2021, 19 patients have been enrolled. Unsupervised hierarchical clustering of the results obtained so far identifies 3 groups of patients, characterized by different profiles of cognitive and behavioral scores. The first cluster is characterized by low Battelle age, high ADOS and low Vineland, RBQ and BPI scores. Low Vineland, RBQ and BPI scores are also detected in the second cluster, which in contrast has high Battelle age and low ADOS scores. The third cluster is somewhat in the middle for the Battelle, Vineland and ADOS scores while displaying the highest levels of aggression (high BPI) and repeated behaviors (high RBQ). In line with the observation that female patients are generally affected by milder forms of autistic symptoms, no male patients are present in the second cluster. Dividing the results by gender highlights that male patients in the third cluster are characterized by a higher frequency of aggression, whereas female patients from the same cluster display a tendency toward higher repetitive behavior. Finally, statistically significant differences in deletion sizes are detected comparing the three clusters (also after correcting for gender), and deletion size appears to be positively correlated with ADOS and negatively correlated with Vineland A and C scores. No correlation is detected between deletion size and the BPI and RBQ scores. Conclusions: Precision medicine may open a new way to understand and treat Central Nervous System disorders. Epigenetic dysregulation has been proposed to be an important mechanism in the pathogenesis of schizophrenia and autism. Vafidemstat holds exciting therapeutic potential in PMS, and this study will provide data regarding the optimal endpoints for a future clinical study to explore vafidemstat ability to treat shank3-associated psychiatric disorders. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=autism" title="autism">autism</a>, <a href="https://publications.waset.org/abstracts/search?q=epigenetics" title=" epigenetics"> epigenetics</a>, <a href="https://publications.waset.org/abstracts/search?q=LSD1" title=" LSD1"> LSD1</a>, <a href="https://publications.waset.org/abstracts/search?q=personalized%20medicine" title=" personalized medicine"> personalized medicine</a> </p> <a href="https://publications.waset.org/abstracts/137638/phenotype-and-psychometric-characterization-of-phelan-mcdermid-syndrome-patients" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/137638.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">165</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">13</span> Characterization of the Lytic Bacteriophage VbɸAB-1 against Drug Resistant Acinetobacter baumannii Isolated from Hospitalized Pressure Ulcers Patients</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=M.%20Doudi">M. Doudi</a>, <a href="https://publications.waset.org/abstracts/search?q=M.%20H.%20Pazandeh"> M. H. Pazandeh</a>, <a href="https://publications.waset.org/abstracts/search?q=L.%20Rahimzadeh%20Torabi"> L. Rahimzadeh Torabi</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Bedsores are pressure ulcers that occur on the skin or tissue due to being immobile and lying in bed for extended periods. Bedsores have the potential to progress into open ulcers, increasing the possibility of variety of bacterial infection. Acinetobacter baumannii, a pathogen of considerable clinical importance, exhibited a significant correlation with Bedsores (pressure ulcers) infections, thereby manifesting a wide spectrum of antibiotic resistance. The emergence of drug resistance has led researchers to focus on alternative methods, particularly phage therapy, for tackling bacterial infections. Phage therapy has emerged as a novel therapeutic approach to regulate the activity of these agents. The management of bacterial infections greatly benefits from the clinical utilization of bacteriophages as a valuable antimicrobial intervention. The primary objective of this investigation consisted of isolating and discerning potent bacteriophage capable of targeting multi drug-resistant (MDR) and extensively drug-resistant (XDR) bacteria obtained from pressure ulcers. In present study, analyzed and isolated A. baumannii strains obtained from a cohort of patients suffering from pressure ulcers at Taleghani Hospital in Ahvaz, Iran. An approach that included biochemical and molecular identification techniques was used to determine the taxonomic classification of bacterial isolates at the genus and species levels. The molecular identification process was facilitated by using the 16S rRNA gene in combination with universal primers 27 F, and 1492 R. Bacteriophage was obtained through the isolation process conducted on treatment plant sewage located in Isfahan, Iran. The main goal of this study was to evaluate different characteristics of phage, such as their appearance, range of hosts they can infect, how quickly they can enter a host, their stability at varying temperatures and pH levels, their effectiveness in killing bacteria, the growth pattern of a single phage stage, mapping of enzymatic digestion, and identification of proteomics patterns. The findings demonstrated that an examination was conducted on a sample of 50 specimens, wherein 15 instances of A. baumannii were identified. These microorganisms are the predominant Gram-negative agents known to cause wound infections in individuals suffering from bedsores. The study's findings indicated a high prevalence of antibiotic resistance in the strains isolated from pressure ulcers, excluding the clinical strains that exhibited responsiveness to colistin.According to the findings obtained from assessments of host range and morphological characteristics of bacteriophage VbɸAB-1, it can be concluded that this phage possesses specificity towards A. Baumannii BAH_Glau1001 was classified as a member of the Plasmaviridae family. The bacteriophage mentioned earlier showed the strongest antibacterial effect at a temperature of 18 °C and a pH of 6.5. Through the utilization of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis on protein fragments, it was established that the bacteriophage VbɸAB-1 exhibited a size range between 50 and 75 kilodaltons (KDa). The numerous research findings on the effectiveness of phages and the safety studies conducted suggest that the phages studied in this research can be considered as a practical solution and recommended approach for controlling and treating stubborn pathogens in burn wounds among hospitalized patients. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=acinetobacter%20baumannii" title="acinetobacter baumannii">acinetobacter baumannii</a>, <a href="https://publications.waset.org/abstracts/search?q=extremely%20drug-%20%20%20%20%20%20resistant" title=" extremely drug- resistant"> extremely drug- resistant</a>, <a href="https://publications.waset.org/abstracts/search?q=phage%20therapy" title=" phage therapy"> phage therapy</a>, <a href="https://publications.waset.org/abstracts/search?q=surgery%20wound" title=" surgery wound"> surgery wound</a> </p> <a href="https://publications.waset.org/abstracts/170538/characterization-of-the-lytic-bacteriophage-vbab-1-against-drug-resistant-acinetobacter-baumannii-isolated-from-hospitalized-pressure-ulcers-patients" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/170538.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">93</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">12</span> Burkholderia Cepacia ST 767 Causing a Three Years Nosocomial Outbreak in a Hemodialysis Unit</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Gousilin%20Leandra%20Rocha%20Da%20Silva">Gousilin Leandra Rocha Da Silva</a>, <a href="https://publications.waset.org/abstracts/search?q=St%C3%A9fani%20T.%20A.%20Dantas"> Stéfani T. A. Dantas</a>, <a href="https://publications.waset.org/abstracts/search?q=Bruna%20F.%20Rossi"> Bruna F. Rossi</a>, <a href="https://publications.waset.org/abstracts/search?q=Erika%20R.%20Bonsaglia"> Erika R. Bonsaglia</a>, <a href="https://publications.waset.org/abstracts/search?q=Ivana%20G.%20Castilho"> Ivana G. Castilho</a>, <a href="https://publications.waset.org/abstracts/search?q=Terue%20Sadatsune"> Terue Sadatsune</a>, <a href="https://publications.waset.org/abstracts/search?q=Ary%20Fernandes%20J%C3%BAnior"> Ary Fernandes Júnior</a>, <a href="https://publications.waset.org/abstracts/search?q=Vera%20l.%20M.%20Rall"> Vera l. M. Rall</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Kidney failure causes decreased diuresis and accumulation of nitrogenous substances in the body. To increase patient survival, hemodialysis is used as a partial substitute for renal function. However, contamination of the water used in this treatment, causing bacteremia in patients, is a worldwide concern. The Burkholderia cepacia complex (Bcc), a group of bacteria with more than 20 species, is frequently isolated from hemodialysis water samples and comprises opportunistic bacteria, affecting immunosuppressed patients, due to its wide variety of virulence factors, in addition to innate resistance to several antimicrobial agents, contributing to the permanence in the hospital environment and to the pathogenesis in the host. The objective of the present work was to characterize molecularly and phenotypically Bcc isolates collected from the water and dialysate of the Hemodialysis Unit and from the blood of patients at a Public Hospital in Botucatu, São Paulo, Brazil, between 2019 and 2021. We used 33 Bcc isolates, previously obtained from blood cultures from patients with bacteremia undergoing hemodialysis treatment (2019-2021) and 24 isolates obtained from water and dialysate samples in a Hemodialysis Unit (same period). The recA gene was sequenced to identify the specific species among the Bcc group. All isolates were tested for the presence of some genes that encode virulence factors such as cblA, esmR, zmpA and zmpB. Considering the epidemiology of the outbreak, the Bcc isolates were molecularly characterized by Multi Locus Sequence Type (MLST) and by pulsed-field gel electrophoresis (PFGE). The verification and quantification of biofilm in a polystyrene microplate were performed by submitting the isolates to different incubation temperatures (20°C, average water temperature and 35°C, optimal temperature for group growth). The antibiogram was performed with disc diffusion tests on agar, using discs impregnated with cefepime (30µg), ceftazidime (30µg), ciprofloxacin (5µg), gentamicin (10µg), imipenem (10µg), amikacin 30µg), sulfametazol/trimethoprim (23.75/1.25µg) and ampicillin/sulbactam (10/10µg). The presence of ZmpB was identified in all isolates, while ZmpA was observed in 96.5% of the isolates, while none of them presented the cblA and esmR genes. The antibiogram of the 33 human isolates indicated that all were resistant to gentamicin, colistin, ampicillin/sulbactam and imipenem. 16 (48.5%) isolates were resistant to amikacin and lower rates of resistance were observed for meropenem, ceftazidime, cefepime, ciprofloxacin and piperacycline/tazobactam (6.1%). All isolates were sensitive to sulfametazol/trimethoprim, levofloxacin and tigecycline. As for the water isolates, resistance was observed only to gentamicin (34.8%) and imipenem (17.4%). According to PFGE results, all isolates obtained from humans and water belonged to the same pulsotype (1), which was identified by recA sequencing as B. cepacia¸, belonging to sequence type ST-767. By observing a single pulse type over three years, one can observe the persistence of this isolate in the pipeline, contaminating patients undergoing hemodialysis, despite the routine disinfection of water with peracetic acid. This persistence is probably due to the production of biofilm, which protects bacteria from disinfectants and, making this scenario more critical, several isolates proved to be multidrug-resistant (resistance to at least three groups of antimicrobials), turning the patient care even more difficult. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=hemodialysis" title="hemodialysis">hemodialysis</a>, <a href="https://publications.waset.org/abstracts/search?q=burkholderia%20cepacia" title=" burkholderia cepacia"> burkholderia cepacia</a>, <a href="https://publications.waset.org/abstracts/search?q=PFGE" title=" PFGE"> PFGE</a>, <a href="https://publications.waset.org/abstracts/search?q=MLST" title=" MLST"> MLST</a>, <a href="https://publications.waset.org/abstracts/search?q=multi%20drug%20resistance" title=" multi drug resistance"> multi drug resistance</a> </p> <a href="https://publications.waset.org/abstracts/159465/burkholderia-cepacia-st-767-causing-a-three-years-nosocomial-outbreak-in-a-hemodialysis-unit" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/159465.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">99</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">11</span> The Lytic Bacteriophage VbɸAB-1 Against Drug-Resistant Acinetobacter Baumannii Isolated from Hospitalized Pressure Ulcers Patients</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=M.%20Doudi">M. Doudi</a>, <a href="https://publications.waset.org/abstracts/search?q=M.%20H.%20Pazandeh"> M. H. Pazandeh</a>, <a href="https://publications.waset.org/abstracts/search?q=L.%20Rahimzadeh%20Torabi"> L. Rahimzadeh Torabi</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Bedsores are pressure ulcers that occur on the skin or tissue due to being immobile and lying in bed for extended periods. Bedsores have the potential to progress into open ulcers, increasing the possibility of a variety of bacterial infections. Acinetobacter baumannii, a pathogen of considerable clinical importance, exhibited a significant correlation with Bedsores (pressure ulcers) infections, thereby manifesting a wide spectrum of antibiotic resistance. The emergence of drug resistance has led researchers to focus on alternative methods, particularly phage therapy, for tackling bacterial infections. Phage therapy has emerged as a novel therapeutic approach to regulate the activity of these agents. The management of bacterial infections greatly benefits from the clinical utilization of bacteriophages as a valuable antimicrobial intervention. The primary objective of this investigation consisted of isolating and discerning potent bacteriophage capable of targeting multi-drug-resistant (MDR) and extensively drug-resistant (XDR) bacteria obtained from pressure ulcers. The present study analyzed and isolated A. baumannii strains obtained from a cohort of patients suffering from pressure ulcers at Taleghani Hospital in Ahvaz, Iran. An approach that included biochemical and molecular identification techniques was used to determine the taxonomic classification of bacterial isolates at the genus and species levels. The molecular identification process was facilitated by using the 16S rRNA gene in combination with universal primers 27 F and 1492 R. Bacteriophage was obtained through the isolation process conducted on treatment plant sewage located in Isfahan, Iran. The main goal of this study was to evaluate different characteristics of phage, such as their appearance, the range of hosts they can infect, how quickly they can enter a host, their stability at varying temperatures and pH levels, their effectiveness in killing bacteria, the growth pattern of a single phage stage, mapping of enzymatic digestion, and identification of proteomics patterns. The findings demonstrated that an examination was conducted on a sample of 50 specimens, wherein 15 instances of A. baumannii were identified. These microorganisms are the predominant Gram-negative agents known to cause wound infections in individuals suffering from bedsores. The study's findings indicated a high prevalence of antibiotic resistance in the strains isolated from pressure ulcers, excluding the clinical strains that exhibited responsiveness to colistin. According to the findings obtained from assessments of host range and morphological characteristics of bacteriophage VbɸAB-1, it can be concluded that this phage possesses specificity towards A. Baumannii BAH_Glau1001 was classified as a member of the Podoviridae family. The bacteriophage mentioned earlier showed the strongest antibacterial effect at a temperature of 18 °C and a pH of 6.5. Through the utilization of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis on protein fragments, it was established that the bacteriophage VbɸAB-1 exhibited a size range between 50 and 75 kilodaltons (KDa). The numerous research findings on the effectiveness of phages and the safety studies conducted suggest that the phages studied in this research can be considered as a practical solution and recommended approach for controlling and treating stubborn pathogens in burn wounds among hospitalized patients. The findings of our research indicated that isolated phages could be an effective antimicrobial and an appreciate candidate for prophylaxis against pressure ulcers. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=acinetobacter%20baumannii" title="acinetobacter baumannii">acinetobacter baumannii</a>, <a href="https://publications.waset.org/abstracts/search?q=extremely%20drug-resistant" title=" extremely drug-resistant"> extremely drug-resistant</a>, <a href="https://publications.waset.org/abstracts/search?q=phage%20therapy" title=" phage therapy"> phage therapy</a>, <a href="https://publications.waset.org/abstracts/search?q=surgery%20wound" title=" surgery wound"> surgery wound</a> </p> <a href="https://publications.waset.org/abstracts/170583/the-lytic-bacteriophage-vbab-1-against-drug-resistant-acinetobacter-baumannii-isolated-from-hospitalized-pressure-ulcers-patients" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/170583.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">90</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">10</span> Antimicrobial and Antioxidant Activities of Actinobacteria Isolated from the Pollen of Pinus sylvestris Grown on the Lake Baikal Shore </h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Denis%20V.%20Axenov-Gribanov">Denis V. Axenov-Gribanov</a>, <a href="https://publications.waset.org/abstracts/search?q=Irina%20V.%20Voytsekhovskaya"> Irina V. Voytsekhovskaya</a>, <a href="https://publications.waset.org/abstracts/search?q=Evgenii%20S.%20Protasov"> Evgenii S. Protasov</a>, <a href="https://publications.waset.org/abstracts/search?q=Maxim%20A.%20%20Timofeyev"> Maxim A. Timofeyev</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Isolated ecosystems existing under specific environmental conditions have been shown to be promising sources of new strains of actinobacteria. The taiga forest of Baikal Siberia has not been well studied, and its actinobacterial population remains uncharacterized. The proximity between the huge water mass of Lake Baikal and high mountain ranges influences the structure and diversity of the plant world in Siberia. Here, we report the isolation of eighteen actinobacterial strains from male cones of Pinus sylvestris trees growing on the shore of the ancient Lake Baikal in Siberia. The actinobacterial strains were isolated on solid nutrient MS media and Czapek agar supplemented with cycloheximide and phosphomycin. Identification of actinobacteria was carried out by 16S rRNA gene sequencing and further analysis of the evolutionary history. Four different liquid and solid media (NL19, DNPM, SG and ISP) were tested for metabolite production. The metabolite extracts produced by the isolated strains were tested for antibacterial and antifungal activities. Also, antiradical activity of crude extracts was carried out. Strain Streptomyces sp. IB 2014 I 74-3 that active against Gram-negative bacteria was selected for dereplication analysis with using the high-yield liquid chromatography with mass-spectrometry. Mass detection was performed in both positive and negative modes, with the detection range set to 160–2500 m/z. Data were collected and analyzed using Bruker Compass Data Analysis software, version 4.1. Dereplication was performed using the Dictionary of Natural Products (DNP) database version 6.1 with the following search parameters: accurate molecular mass, absorption spectra and source of compound isolation. Thus, in addition to more common representative strains of Streptomyces, several species belonging to the genera Rhodococcus, Amycolatopsis, and Micromonospora were isolated. Several of the selected strains were deposited in the Russian Collection of Agricultural Microorganisms (RCAM), St. Petersburg, Russia. All isolated strains exhibited antibacterial and antifungal activities. We identified several strains that inhibited the growth of the pathogen Candida albicans but did not hinder the growth of Saccharomyces cerevisiae. Several isolates were active against Gram-positive and Gram-negative bacteria. Moreover, extracts of several strains demonstrated high antioxidant activity. The high proportion of biologically active strains producing antibacterial and specific antifungal compounds may reflect their role in protecting pollen against phytopathogens. Dereplication of the secondary metabolites of the strain Streptomyces sp. IB 2014 I 74-3 was resulted in the fact that a total of 59 major compounds were detected in the culture liquid extract of strain cultivated in ISP medium. Eight compounds were preliminarily identified based on characteristics described in the Dictionary of Natural Products database, using the search parameters Streptomyces sp. IB 2014 I 74-3 was found to produce saframycin A, Y3 and S; 2-amino-3-oxo-3H-phenoxazine-1,8-dicarboxylic acid; galtamycinone; platencin A4-13R and A4-4S; ganefromycin d1; the antibiotic SS 8201B; and streptothricin D, 40-decarbamoyl, 60-carbamoyl. Moreover, forty-nine of the 59 compounds detected in the extract examined in the present study did not result in any positive hits when searching within the DNP database and could not be identified based on available mass-spec data. Thus, these compounds might represent new findings. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=actinobacteria" title="actinobacteria">actinobacteria</a>, <a href="https://publications.waset.org/abstracts/search?q=Baikal%20Lake" title=" Baikal Lake"> Baikal Lake</a>, <a href="https://publications.waset.org/abstracts/search?q=biodiversity" title=" biodiversity"> biodiversity</a>, <a href="https://publications.waset.org/abstracts/search?q=male%20cones" title=" male cones"> male cones</a>, <a href="https://publications.waset.org/abstracts/search?q=Pinus%20sylvestris" title=" Pinus sylvestris"> Pinus sylvestris</a> </p> <a href="https://publications.waset.org/abstracts/55755/antimicrobial-and-antioxidant-activities-of-actinobacteria-isolated-from-the-pollen-of-pinus-sylvestris-grown-on-the-lake-baikal-shore" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/55755.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">232</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">9</span> Efficacy of Solanum anguivi Lam Fruits (African Bitter Berry) in Lowering Glucose Levels in Diabetes Mellitus and Increasing Survival</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Aisha%20Musaazi%20Sebunya%20Nakitto">Aisha Musaazi Sebunya Nakitto</a>, <a href="https://publications.waset.org/abstracts/search?q=Anika%20E.%20Wagner"> Anika E. Wagner</a>, <a href="https://publications.waset.org/abstracts/search?q=Yusuf%20B.%20Byaruhanga"> Yusuf B. Byaruhanga</a>, <a href="https://publications.waset.org/abstracts/search?q=John%20H.%20Muyonga"> John H. Muyonga</a> </p> <p class="card-text"><strong>Abstract:</strong></p> The prevalence and burden of diabetes are rapidly increasing globally, stemming from changes in lifestyle and dietary habits. Although several drugs are available to treat type 2 diabetes mellitus (T2DM), many are accompanied by several side effects and are often costly. Solanum anguivi Lam. fruits (SALF) are bitter berries that commonly grow in the wild and are traditionally cultivated by many globally as a remedy for T2DM. This effect is likely attributable to the presence of bioactive compounds such as phenolics, flavonoids, saponins, alkaloids, and vitamin C in SALF. In this study, we investigated the morphological characteristics of different SALF accessions and the effect of ripeness stages and thermal treatments on the bioactive compounds contents (BCC) and antioxidant activity (AA) of SALF accessions. Using the fruit fly Drosophila melanogaster (D. melanogaster) model, we explored the potential impact of dietary SALF in preventing and treating T2DM phenotypes. Morphological characterization was conducted based on descriptors of Solanum species. The BCC and AA of SALF at different ripeness stages (unripe, yellow, orange, and red) and after thermal treatments were determined using spectrophotometry, HPLC, and gravimetry. Male and female fruit flies were fed a high-sugar diet (HSD) to induce a T2DM-like phenotype, while control flies were fed on SY10 medium for up to 24 days. Experimental flies were exposed to HSD supplemented with 5 or 10 mg/ml SALF. The therapeutic and prevention effect of SALF in T2DM-like phenotype was investigated on weight, climbing activity, glucose and triglyceride contents, survival, and gene expression of PPARγ co-activator 1α fly homolog Srl and Drosophila insulin-like peptides. Methods in fly studies included Gustatory assay, Climbing assay, Glucose GOD-PAP assay, Triglyceride GPO-PAP assay, Roti-Quant®, and Real Time-PCR analysis. The ripeness stage significantly influenced SALF BCC and AA, and this was dependent on the accession. The unripe stage had the highest AA and total phenolics and flavonoids; the orange stage was rich in saponins, while the red stage had the highest alkaloid contents. Boiling and steaming increased the total phenolics and AA up to 4-fold and 3-fold, respectively. Drying at low temperatures resulted in higher phenolics and AA than the control. In the therapeutic model, the HSD-fed female flies exhibited elevated glucose levels, which exhibited a dose-dependent reduction upon exposure to a SALF-supplemented diet. Female flies fed on a SALF+ HSD exhibited a significant increase in survival compared to HSD-fed and control diet-fed flies. SALF supplementation did not alter the weights, fitness, and triglyceride levels of female flies in comparison with HSD-only-fed flies. The mRNA levels of Srl decreased in HSD-fed flies compared to the control-fed, with no effect observed in females exposed to HSD+SALF. Similarly, in the preventative model, the SALF diet resulted in higher survival of supplemented flies compared to controls. Consumption of boiled unripe SALF may result in the highest health benefits due to the high phenolic contents and antioxidant activity observed. Dietary intake of SALF significantly lowered glucose levels and increased survival of the D. melanogaster model. Additional studies in higher organisms are needed to explore the preventative and therapeutic potential of SALF in T2DM. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=antioxidant%20activity" title="antioxidant activity">antioxidant activity</a>, <a href="https://publications.waset.org/abstracts/search?q=bioactive%20compounds" title=" bioactive compounds"> bioactive compounds</a>, <a href="https://publications.waset.org/abstracts/search?q=bitter%20berries" title=" bitter berries"> bitter berries</a>, <a href="https://publications.waset.org/abstracts/search?q=Drosophila%20melanogaster" title=" Drosophila melanogaster"> Drosophila melanogaster</a>, <a href="https://publications.waset.org/abstracts/search?q=Solanum%20anguivi" title=" Solanum anguivi"> Solanum anguivi</a>, <a href="https://publications.waset.org/abstracts/search?q=type%202%20diabetes%20mellitus" title=" type 2 diabetes mellitus"> type 2 diabetes mellitus</a>, <a href="https://publications.waset.org/abstracts/search?q=survival" title=" survival"> survival</a> </p> <a href="https://publications.waset.org/abstracts/190336/efficacy-of-solanum-anguivi-lam-fruits-african-bitter-berry-in-lowering-glucose-levels-in-diabetes-mellitus-and-increasing-survival" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/190336.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">30</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">8</span> The Pro-Reparative Effect of Vasoactive Intestinal Peptide in Chronic Inflammatory Osteolytic Periapical Lesions</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Michelle%20C.%20S.%20Azevedo">Michelle C. S. Azevedo</a>, <a href="https://publications.waset.org/abstracts/search?q=Priscila%20M.%20Colavite"> Priscila M. Colavite</a>, <a href="https://publications.waset.org/abstracts/search?q=Carolina%20F.%20Francisconi"> Carolina F. Francisconi</a>, <a href="https://publications.waset.org/abstracts/search?q=Ana%20P.%20Trombone"> Ana P. Trombone</a>, <a href="https://publications.waset.org/abstracts/search?q=Gustavo%20P.%20Garlet"> Gustavo P. Garlet</a> </p> <p class="card-text"><strong>Abstract:</strong></p> VIP (vasoactive intestinal peptide) know as a potential protective factor in the view of its marked immunosuppressive properties. In this work, we investigated a possible association of VIP with the clinical status of experimental periapical granulomas and the association with expression markers in the lesions potentially associated with periapical lesions pathogenesis. C57BL/6WT mice were treated or not with recombinant VIP. Animals with active/progressive (N=40), inactive/stable (N=70) periapical granulomas and controls (N=50) were anesthetized and the right mandibular first molar was surgically opened, allowing exposure of dental pulp. Endodontic pathogenic bacterial strains were inoculated: Porphyromonas gingivalis, Prevotella nigrescens, Actinomyces viscosus, and Fusobacterium nucleatum subsp. polymorphum. The cavity was not sealed after bacterial inoculation. During lesion development, animals were treated or not with recombinant VIP 3 days post infection. Animals were killed after 3, 7, 14, and 21 days of infection and the jaws were dissected. The extraction of total RNA from periodontal tissues was performed and the integrity of samples was checked. qPCR reaction using TaqMan chemistry with inventoried primers were performed in ViiA7 equipment. The results, depicted as the relative levels of gene expression, were calculated in reference to GAPDH and β-actin expression. Periodontal tissues from upper molars were vested and incubated supplemented RPMI, followed by processing with 0.05% DNase. Cell viability and couting were determined by Neubauer chamber analysis. For flow cytometry analysis, after cell counting the cells were stained with the optimal dilution of each antibody; (PE)-conjugated and (FITC)-conjugated antibodies against CD4, CD25, FOXP3, IL-4, IL-17 and IFN-γ antibodies, as well their respective isotype controls. Cells were analyzed by FACScan and CellQuest software. Results are presented as the number of cells in the periodontal tissues or the number of positive cells for each marker in the CD4+FOXp3+, CD4+IL-4+, CD4+IFNg+ and CD4+IL-17+ subpopulations. The levels mRNA were measured by qPCR. The VIP expression was predominated in inactive lesions, as well part of the clusters of cytokine/Th markers identified as protective factors and a negative correlation between VIP expression and lesion evolution was observed. A quantitative analysis of IL1β, IL17, TNF, IFN, MMP2, RANKL, OPG, IL10, TGFβ, CTLA4, COL5A1, CTGF, CXCL11, FGF7, ITGA4, ITGA5, SERP1 and VTN expression was measured in experimental periapical lesions treated with VIP 7 and 14 days after lesion induction and healthy animals. After 7 days, all targets presented a significate increase in comparison to untreated animals. About migration kinetics, profile of chemokine receptors expression of TCD4+ subsets and phenotypic analysis of Tregs, Th1, Th2 and Th17 cells during the course of experimental periodontal disease evaluated by flow cytometry and depicted as the number of positive cells for each marker. CD4+IFNg+ and CD4+FOXp3+ cells migration were significate increased 7 days post VIP treatment. CD4+IL17+ cells migration were significate increased 7 and 14 days post VIP treatment, CD4+IL4+ cells migration were significate increased 14 and 21 days post VIP treatment compared to the control group. In conclusion, our experimental data support VIP involvement in determining the inactivity of periapical lesions. Financial support: FAPESP #2015/25618-2. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=chronic%20inflammation" title="chronic inflammation">chronic inflammation</a>, <a href="https://publications.waset.org/abstracts/search?q=cytokines" title=" cytokines"> cytokines</a>, <a href="https://publications.waset.org/abstracts/search?q=osteolytic%20lesions" title=" osteolytic lesions"> osteolytic lesions</a>, <a href="https://publications.waset.org/abstracts/search?q=VIP%20%28Vasoactive%20Intestinal%20Peptide%29" title=" VIP (Vasoactive Intestinal Peptide)"> VIP (Vasoactive Intestinal Peptide)</a> </p> <a href="https://publications.waset.org/abstracts/76218/the-pro-reparative-effect-of-vasoactive-intestinal-peptide-in-chronic-inflammatory-osteolytic-periapical-lesions" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/76218.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">193</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">7</span> Prospects of Acellular Organ Scaffolds for Drug Discovery</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Inna%20Kornienko">Inna Kornienko</a>, <a href="https://publications.waset.org/abstracts/search?q=Svetlana%20Guryeva"> Svetlana Guryeva</a>, <a href="https://publications.waset.org/abstracts/search?q=Natalia%20Danilova"> Natalia Danilova</a>, <a href="https://publications.waset.org/abstracts/search?q=Elena%20Petersen"> Elena Petersen</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Drug toxicity often goes undetected until clinical trials, the most expensive and dangerous phase of drug development. Both human cell culture and animal studies have limitations that cannot be overcome by improvements in drug testing protocols. Tissue engineering is an emerging alternative approach to creating models of human malignant tumors for experimental oncology, personalized medicine, and drug discovery studies. This new generation of bioengineered tumors provides an opportunity to control and explore the role of every component of the model system including cell populations, supportive scaffolds, and signaling molecules. An area that could greatly benefit from these models is cancer research. Recent advances in tissue engineering demonstrated that decellularized tissue is an excellent scaffold for tissue engineering. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. Decellularized Organs preserve organ microenvironment, which is critical for cancer metastasis. Utilizing 3D tumor models results greater proximity of cell culture morphological characteristics in a model to its in vivo counterpart, allows more accurate simulation of the processes within a functioning tumor and its pathogenesis. 3D models allow study of migration processes and cell proliferation with higher reliability as well. Moreover, cancer cells in a 3D model bear closer resemblance to living conditions in terms of gene expression, cell surface receptor expression, and signaling. 2D cell monolayers do not provide the geometrical and mechanical cues of tissues in vivo and are, therefore, not suitable to accurately predict the responses of living organisms. 3D models can provide several levels of complexity from simple monocultures of cancer cell lines in liquid environment comprised of oxygen and nutrient gradients and cell-cell interaction to more advanced models, which include co-culturing with other cell types, such as endothelial and immune cells. Following this reasoning, spheroids cultivated from one or multiple patient-derived cell lines can be utilized to seed the matrix rather than monolayer cells. This approach furthers the progress towards personalized medicine. As an initial step to create a new ex vivo tissue engineered model of a cancer tumor, optimized protocols have been designed to obtain organ-specific acellular matrices and evaluate their potential as tissue engineered scaffolds for cultures of normal and tumor cells. Decellularized biomatrix was prepared from animals’ kidneys, urethra, lungs, heart, and liver by two decellularization methods: perfusion in a bioreactor system and immersion-agitation on an orbital shaker with the use of various detergents (SDS, Triton X-100) in different concentrations and freezing. Acellular scaffolds and tissue engineered constructs have been characterized and compared using morphological methods. Models using decellularized matrix have certain advantages, such as maintaining native extracellular matrix properties and biomimetic microenvironment for cancer cells; compatibility with multiple cell types for cell culture and drug screening; utilization to culture patient-derived cells in vitro to evaluate different anticancer therapeutics for developing personalized medicines. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=3D%20models" title="3D models">3D models</a>, <a href="https://publications.waset.org/abstracts/search?q=decellularization" title=" decellularization"> decellularization</a>, <a href="https://publications.waset.org/abstracts/search?q=drug%20discovery" title=" drug discovery"> drug discovery</a>, <a href="https://publications.waset.org/abstracts/search?q=drug%20toxicity" title=" drug toxicity"> drug toxicity</a>, <a href="https://publications.waset.org/abstracts/search?q=scaffolds" title=" scaffolds"> scaffolds</a>, <a href="https://publications.waset.org/abstracts/search?q=spheroids" title=" spheroids"> spheroids</a>, <a href="https://publications.waset.org/abstracts/search?q=tissue%20engineering" title=" tissue engineering"> tissue engineering</a> </p> <a href="https://publications.waset.org/abstracts/65635/prospects-of-acellular-organ-scaffolds-for-drug-discovery" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/65635.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">301</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">6</span> Enhanced Bioproduction of Moscatilin in Dendrobium ovatum through Hairy Root Culture</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Ipsita%20Pujari">Ipsita Pujari</a>, <a href="https://publications.waset.org/abstracts/search?q=Abitha%20Thomas"> Abitha Thomas</a>, <a href="https://publications.waset.org/abstracts/search?q=Vidhu%20S.%20Babu"> Vidhu S. Babu</a>, <a href="https://publications.waset.org/abstracts/search?q=K.%20Satyamoorthy"> K. Satyamoorthy</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Orchids are esteemed as celebrities in cut flower industry globally, due to their long-lasting fragrance and freshness. Apart from splendor, the unique metabolites endowed with pharmaceutical potency have made them one of the most hunted in plant kingdom. This had led to their trafficking, resulting in habitat loss, subsequently making them occupiers of IUCN red list as RET species. Many of the orchids especially wild varieties still remain undiscovered. In view to protect and conserve the wild germplasm, researchers have been inventing novel micropropagation protocols; thereby conserving Orchids. India is overflowing with exclusive wild cultivars of Orchids, whose pharmaceutical properties remain untapped and are not marketed owing to relatively small flowers. However, their germplasm is quite pertinent to be preserved for making unusual hybrids. Dendrobium genus is the second largest among Orchids exists in India and has highest demand attributable to enduring cut flowers and significant therapeutic uses in traditional medicinal system. Though the genus is quite endemic in Western Ghat regions of the country, many species are still anonymous with their unknown curative properties. A standard breeding cycle in Orchids usually takes five to seven years (Dendrobium hybrids taking a long juvenile phase of two to five years reaching maturity and flowering stage) and this extensive life cycle has always hindered the development of Dendrobium breeding. Dendrobium is reported with essential therapeutic plant bio-chemicals and ‘Moscatilin’ is one, found exclusive to this famous Dendrobium genus. Moscatilin is reported to have anti-mutagenic and anti-cancer properties, whose positive action has very recently been demonstrated against a range of cancers. Our preliminary study here established a simple and economic small-scale propagation protocol of Dendrobium ovatum describing in vitro production of Moscatilin. Subsequently for enhancing the content of Moscatilin, an efficient experimental related to the organization of transgenic (hairy) D. ovatum root cultures through infection of Agrobacterium rhizogenes 2364 strain on MS basal medium is being reported in the present study. Hairy roots generated on almost half of the explants used (spherules, in vitro plantlets and calli) maintained through suspension cultures, after 8 weeks of co-cultivation with Agrobacterium rhizogenes. GFP assay performed with isolated hairy roots has confirmed the integrative transformation which was further positively confirmed by PCR using rolB gene specific primers. Reverse phase-high performance liquid chromatography and mass spectrometry techniques were used for quantification and accurate identification of Moscatilin respectively from transgenic systems. A noticeable ~3 fold increase in contents were observed in transformed D. ovatum root cultures as compared to the simple in vitro culture, callus culture and callus regeneration plantlets. Role of elicitors e.g., Methyl jasmonate, Salicylic acid, Yeast extract and Chitosan were tested for elevating the Moscatilin content to obtain a comprehensive optimized protocol facilitating the in vitro production of valuable Moscatilin with larger yield. This study would provide evidence towards the in vitro assembly of Moscatilin within a short time-period through not a so-expensive technology for the first time. It also serves as an appropriate basis for bioreactor scale-up resulting in commercial bioproduction of Moscatilin. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=bioproduction" title="bioproduction">bioproduction</a>, <a href="https://publications.waset.org/abstracts/search?q=Dendrobium%20ovatum" title=" Dendrobium ovatum"> Dendrobium ovatum</a>, <a href="https://publications.waset.org/abstracts/search?q=hairy%20root%20culture" title=" hairy root culture"> hairy root culture</a>, <a href="https://publications.waset.org/abstracts/search?q=moscatilin" title=" moscatilin"> moscatilin</a> </p> <a href="https://publications.waset.org/abstracts/44011/enhanced-bioproduction-of-moscatilin-in-dendrobium-ovatum-through-hairy-root-culture" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/44011.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">238</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">5</span> The Use of Rule-Based Cellular Automata to Track and Forecast the Dispersal of Classical Biocontrol Agents at Scale, with an Application to the Fopius arisanus Fruit Fly Parasitoid</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Agboka%20Komi%20Mensah">Agboka Komi Mensah</a>, <a href="https://publications.waset.org/abstracts/search?q=John%20Odindi"> John Odindi</a>, <a href="https://publications.waset.org/abstracts/search?q=Elfatih%20M.%20Abdel-Rahman"> Elfatih M. Abdel-Rahman</a>, <a href="https://publications.waset.org/abstracts/search?q=Onisimo%20Mutanga"> Onisimo Mutanga</a>, <a href="https://publications.waset.org/abstracts/search?q=Henri%20Ez%20Tonnang"> Henri Ez Tonnang</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Ecosystems are networks of organisms and populations that form a community of various species interacting within their habitats. Such habitats are defined by abiotic and biotic conditions that establish the initial limits to a population's growth, development, and reproduction. The habitat’s conditions explain the context in which species interact to access resources such as food, water, space, shelter, and mates, allowing for feeding, dispersal, and reproduction. Dispersal is an essential life-history strategy that affects gene flow, resource competition, population dynamics, and species distributions. Despite the importance of dispersal in population dynamics and survival, understanding the mechanism underpinning the dispersal of organisms remains challenging. For instance, when an organism moves into an ecosystem for survival and resource competition, its progression is highly influenced by extrinsic factors such as its physiological state, climatic variables and ability to evade predation. Therefore, greater spatial detail is necessary to understand organism dispersal dynamics. Understanding organisms dispersal can be addressed using empirical and mechanistic modelling approaches, with the adopted approach depending on the study's purpose Cellular automata (CA) is an example of these approaches that have been successfully used in biological studies to analyze the dispersal of living organisms. Cellular automata can be briefly described as occupied cells by an individual that evolves based on proper decisions based on a set of neighbours' rules. However, in the ambit of modelling individual organisms dispersal at the landscape scale, we lack user friendly tools that do not require expertise in mathematical models and computing ability; such as a visual analytics framework for tracking and forecasting the dispersal behaviour of organisms. The term "visual analytics" (VA) describes a semiautomated approach to electronic data processing that is guided by users who can interact with data via an interface. Essentially, VA converts large amounts of quantitative or qualitative data into graphical formats that can be customized based on the operator's needs. Additionally, this approach can be used to enhance the ability of users from various backgrounds to understand data, communicate results, and disseminate information across a wide range of disciplines. To support effective analysis of the dispersal of organisms at the landscape scale, we therefore designed Pydisp which is a free visual data analytics tool for spatiotemporal dispersal modeling built in Python. Its user interface allows users to perform a quick and interactive spatiotemporal analysis of species dispersal using bioecological and climatic data. Pydisp enables reuse and upgrade through the use of simple principles such as Fuzzy cellular automata algorithms. The potential of dispersal modeling is demonstrated in a case study by predicting the dispersal of Fopius arisanus (Sonan), endoparasitoids to control Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) in Kenya. The results obtained from our example clearly illustrate the parasitoid's dispersal process at the landscape level and confirm that dynamic processes in an agroecosystem are better understood when designed using mechanistic modelling approaches. Furthermore, as demonstrated in the example, the built software is highly effective in portraying the dispersal of organisms despite the unavailability of detailed data on the species dispersal mechanisms. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=cellular%20automata" title="cellular automata">cellular automata</a>, <a href="https://publications.waset.org/abstracts/search?q=fuzzy%20logic" title=" fuzzy logic"> fuzzy logic</a>, <a href="https://publications.waset.org/abstracts/search?q=landscape" title=" landscape"> landscape</a>, <a href="https://publications.waset.org/abstracts/search?q=spatiotemporal" title=" spatiotemporal"> spatiotemporal</a> </p> <a href="https://publications.waset.org/abstracts/161359/the-use-of-rule-based-cellular-automata-to-track-and-forecast-the-dispersal-of-classical-biocontrol-agents-at-scale-with-an-application-to-the-fopius-arisanus-fruit-fly-parasitoid" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/161359.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">77</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">4</span> Large-scale GWAS Investigating Genetic Contributions to Queerness Will Decrease Stigma Against LGBTQ+ Communities</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Paul%20J.%20McKay">Paul J. McKay</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Large-scale genome-wide association studies (GWAS) investigating genetic contributions to sexual orientation and gender identity are largely lacking and may reduce stigma experienced in the LGBTQ+ community by providing an underlying biological explanation for queerness. While there is a growing consensus within the scientific community that genetic makeup contributes – at least in part – to sexual orientation and gender identity, there is a marked lack of genomics research exploring polygenic contributions to queerness. Based on recent (2019) findings from a large-scale GWAS investigating the genetic architecture of same-sex sexual behavior, and various additional peer-reviewed publications detailing novel insights into the molecular mechanisms of sexual orientation and gender identity, we hypothesize that sexual orientation and gender identity are complex, multifactorial, and polygenic; meaning that many genetic factors contribute to these phenomena, and environmental factors play a possible role through epigenetic modulation. In recent years, large-scale GWAS studies have been paramount to our modern understanding of many other complex human traits, such as in the case of autism spectrum disorder (ASD). Despite possible benefits of such research, including reduced stigma towards queer people, improved outcomes for LGBTQ+ in familial, socio-cultural, and political contexts, and improved access to healthcare (particularly for trans populations); important risks and considerations remain surrounding this type of research. To mitigate possibilities such as invalidation of the queer identities of existing LGBTQ+ individuals, genetic discrimination, or the possibility of euthanasia of embryos with a genetic predisposition to queerness (through reproductive technologies like IVF and/or gene-editing in utero), we propose a community-engaged research (CER) framework which emphasizes the privacy and confidentiality of research participants. Importantly, the historical legacy of scientific research attempting to pathologize queerness (in particular, falsely equating gender variance to mental illness) must be acknowledged to ensure any future research conducted in this realm does not propagate notions of homophobia, transphobia or stigma against queer people. Ultimately, in a world where same-sex sexual activity is criminalized in 69 UN member states, with 67 of these states imposing imprisonment, 8 imposing public flogging, 6 (Brunei, Iran, Mauritania, Nigeria, Saudi Arabia, Yemen) invoking the death penalty, and another 5 (Afghanistan, Pakistan, Qatar, Somalia, United Arab Emirates) possibly invoking the death penalty, the importance of this research cannot be understated, as finding a biological basis for queerness would directly oppose the harmful rhetoric that “being LGBTQ+ is a choice.” Anti-trans legislation is similarly widespread: In the United States in 2022 alone (as of Oct. 13), 155 anti-trans bills have been introduced preventing trans girls and women from playing on female sports teams, barring trans youth from using bathrooms and locker rooms that align with their gender identity, banning access to gender affirming medical care (e.g., hormone-replacement therapy, gender-affirming surgeries), and imposing legal restrictions on name changes. Understanding that a general lack of knowledge about the biological basis of queerness may be a contributing factor to the societal stigma faced by gender and sexual orientation minorities, we propose the initiation of large-scale GWAS studies investigating the genetic basis of gender identity and sexual orientation. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=genome-wide%20association%20studies%20%28GWAS%29" title="genome-wide association studies (GWAS)">genome-wide association studies (GWAS)</a>, <a href="https://publications.waset.org/abstracts/search?q=sexual%20and%20gender%20minorities%20%28SGM%29" title=" sexual and gender minorities (SGM)"> sexual and gender minorities (SGM)</a>, <a href="https://publications.waset.org/abstracts/search?q=polygenicity" title=" polygenicity"> polygenicity</a>, <a href="https://publications.waset.org/abstracts/search?q=community-engaged%20research%20%28CER%29" title=" community-engaged research (CER)"> community-engaged research (CER)</a> </p> <a href="https://publications.waset.org/abstracts/159108/large-scale-gwas-investigating-genetic-contributions-to-queerness-will-decrease-stigma-against-lgbtq-communities" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/159108.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">69</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">3</span> Morphological and Molecular Abnormalities of the Skeletal Muscle Tissue from Pediatric Patient Affected by a Rare Genetic Chaperonopathy Associated with Motor Neuropathy</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Leila%20Noori">Leila Noori</a>, <a href="https://publications.waset.org/abstracts/search?q=Rosario%20Barone"> Rosario Barone</a>, <a href="https://publications.waset.org/abstracts/search?q=Francesca%20Rappa"> Francesca Rappa</a>, <a href="https://publications.waset.org/abstracts/search?q=Antonella%20Marino%20Gammazza"> Antonella Marino Gammazza</a>, <a href="https://publications.waset.org/abstracts/search?q=Alessandra%20Maria%20Vitale"> Alessandra Maria Vitale</a>, <a href="https://publications.waset.org/abstracts/search?q=Giuseppe%20Donato%20Mangano"> Giuseppe Donato Mangano</a>, <a href="https://publications.waset.org/abstracts/search?q=Giusy%20Sentiero"> Giusy Sentiero</a>, <a href="https://publications.waset.org/abstracts/search?q=Filippo%20Macaluso"> Filippo Macaluso</a>, <a href="https://publications.waset.org/abstracts/search?q=Kathryn%20H.%20Myburgh"> Kathryn H. Myburgh</a>, <a href="https://publications.waset.org/abstracts/search?q=Francesco%20Cappello"> Francesco Cappello</a>, <a href="https://publications.waset.org/abstracts/search?q=Federica%20Scalia"> Federica Scalia</a> </p> <p class="card-text"><strong>Abstract:</strong></p> The neuromuscular system controls, directs, and allows movement of the body through the action of neural circuits, which include motor neurons, sensory neurons, and skeletal muscle fibers. Protein homeostasis of the involved cytotypes appears crucial to maintain the correct and prolonged functions of the neuromuscular system, and both neuronal cells and skeletal muscle fibers express significant quantities of protein chaperones, the molecular machinery responsible to maintain the protein turnover. Genetic mutations or defective post-translational modifications of molecular chaperones (i.e., genetic or acquired chaperonopathies) may lead to neuromuscular disorders called as neurochaperonopathies. The limited knowledge of the effects of the defective chaperones on skeletal muscle fibers and neurons impedes the progression of therapeutic approaches. A distinct genetic variation of CCT5 gene encoding for the subunit 5 of the chaperonin CCT (Chaperonin Containing TCP1; also known as TRiC, TCP1 Ring Complex) was recently described associated with severe distal motor neuropathy by our team. In this study, we investigated the histopathological abnormalities of the skeletal muscle biopsy of the pediatric patient affected by the mutation Leu224Val in the CCT5 subunit. We provide molecular and structural features of the diseased skeletal muscle tissue that we believe may be useful to identify undiagnosed cases of this rare genetic disorder. We investigated the histological abnormalities of the affected tissue via hematoxylin and eosin staining. Then we used immunofluorescence and qPCR techniques to explore the expression and distribution of CCT5 in diseased and healthy skeletal muscle tissue. Immunofluorescence and immunohistochemistry assays were performed to study the sarcomeric and structural proteins of skeletal muscle, including actin, myosin, tubulin, troponin-T, telethonin, and titin. We performed Western blot to examine the protein expression of CCT5 and some heat shock proteins, Hsp90, Hsp60, Hsp27, and α-B crystallin, along with the main client proteins of the CCT5, actin, and tubulin. Our findings revealed muscular atrophy, abnormal morphology, and different sizes of muscle fibers in affected tissue. The swollen nuclei and wide interfiber spaces were seen. Expression of CCT5 had been decreased and showed a different distribution pattern in the affected tissue. Altered expression, distribution, and bandage pattern were detected by confocal microscopy for the interested muscular proteins in tissue from the patient compared to the healthy control. Protein levels of the studied Hsps normally located at the Z-disk were reduced. Western blot results showed increased levels of the actin and tubulin proteins in the diseased skeletal muscle biopsy compared to healthy tissue. Chaperones must be expressed at high levels in skeletal muscle to counteract various stressors such as mechanical, oxidative, and thermal crises; therefore, it seems relevant that defects of molecular chaperones may result in damaged skeletal muscle fibers. So far, several chaperones or cochaperones involved in neuromuscular disorders have been defined. Our study shows that alteration of the CCT5 subunit is associated with the damaged structure of skeletal muscle fibers and alterations of chaperone system components and paves the way to explore possible alternative substrates of chaperonin CCT. However, further studies are underway to investigate the CCT mechanisms of action to design applicable therapeutic strategies. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=molecular%20chaperones" title="molecular chaperones">molecular chaperones</a>, <a href="https://publications.waset.org/abstracts/search?q=neurochaperonopathy" title=" neurochaperonopathy"> neurochaperonopathy</a>, <a href="https://publications.waset.org/abstracts/search?q=neuromuscular%20system" title=" neuromuscular system"> neuromuscular system</a>, <a href="https://publications.waset.org/abstracts/search?q=protein%20homeostasis" title=" protein homeostasis"> protein homeostasis</a> </p> <a href="https://publications.waset.org/abstracts/161075/morphological-and-molecular-abnormalities-of-the-skeletal-muscle-tissue-from-pediatric-patient-affected-by-a-rare-genetic-chaperonopathy-associated-with-motor-neuropathy" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/161075.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">71</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">2</span> Exploring Factors That May Contribute to the Underdiagnosis of Hereditary Transthyretin Amyloidosis in African American Patients</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Kelsi%20Hagerty">Kelsi Hagerty</a>, <a href="https://publications.waset.org/abstracts/search?q=Ami%20Rosen"> Ami Rosen</a>, <a href="https://publications.waset.org/abstracts/search?q=Aaliyah%20Heyward"> Aaliyah Heyward</a>, <a href="https://publications.waset.org/abstracts/search?q=Nadia%20Ali"> Nadia Ali</a>, <a href="https://publications.waset.org/abstracts/search?q=Emily%20Brown"> Emily Brown</a>, <a href="https://publications.waset.org/abstracts/search?q=Erin%20Demo"> Erin Demo</a>, <a href="https://publications.waset.org/abstracts/search?q=Yue%20Guan"> Yue Guan</a>, <a href="https://publications.waset.org/abstracts/search?q=Modele%20Ogunniyi"> Modele Ogunniyi</a>, <a href="https://publications.waset.org/abstracts/search?q=Brianna%20McDaniels"> Brianna McDaniels</a>, <a href="https://publications.waset.org/abstracts/search?q=Alanna%20Morris"> Alanna Morris</a>, <a href="https://publications.waset.org/abstracts/search?q=Kunal%20Bhatt"> Kunal Bhatt</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Hereditary transthyretin amyloidosis (hATTR) is a progressive, multi-systemic, and life-threatening disease caused by a disruption in the TTR protein that delivers thyroxine and retinol to the liver. This disruption causes the protein to misfold into amyloid fibrils, leading to the accumulation of the amyloid fibrils in the heart, nerves, and GI tract. Over 130 variants in the TTR gene are known to cause hATTR. The Val122Ile variant is the most common in the United States and is seen almost exclusively in people of African descent. TTR variants are inherited in an autosomal dominant fashion and have incomplete penetrance and variable expressivity. Individuals with hATTR may exhibit symptoms from as early as 30 years to as late as 80 years of age. hATTR is characterized by a wide range of clinical symptoms such as cardiomyopathy, neuropathy, carpal tunnel syndrome, and GI complications. Without treatment, hATTR leads to progressive disease and can ultimately lead to heart failure. hATTR disproportionately affects individuals of African descent; the estimated prevalence of hATTR among Black individuals in the US is 3.4%. Unfortunately, hATTR is often underdiagnosed and misdiagnosed because many symptoms of the disease overlap with other cardiac conditions. Due to the progressive nature of the disease, multi-systemic manifestations that can lead to a shortened lifespan, and the availability of free genetic testing and promising FDA-approved therapies that enhance treatability, early identification of individuals with a pathogenic hATTR variant is important, as this can significantly impact medical management for patients and their relatives. Furthermore, recent literature suggests that TTR genetic testing should be performed in all patients with suspicion of TTR-related cardiomyopathy, regardless of age, and that follow-up with genetic counseling services is recommended. Relatives of patients with hATTR benefit from genetic testing because testing can identify carriers early and allow relatives to receive regular screening and management. Despite the striking prevalence of hATTR among Black individuals, hATTR remains underdiagnosed in this patient population, and germline genetic testing for hATTR in Black individuals seems to be underrepresented, though the reasons for this have not yet been brought to light. Historically, Black patients experience a number of barriers to seeking healthcare that has been hypothesized to perpetuate the underdiagnosis of hATTR, such as lack of access and mistrust of healthcare professionals. Prior research has described a myriad of factors that shape an individual’s decision about whether to pursue presymptomatic genetic testing for a familial pathogenic variant, such as family closeness and communication, family dynamics, and a desire to inform other family members about potential health risks. This study explores these factors through 10 in-depth interviews with patients with hATTR about what factors may be contributing to the underdiagnosis of hATTR in the Black population. Participants were selected from the Emory University Amyloidosis clinic based on having a molecular diagnosis of hATTR. Interviews were recorded and transcribed verbatim, then coded using MAXQDA software. Thematic analysis was completed to draw commonalities between participants. Upon preliminary analysis, several themes have emerged. Barriers identified include i) Misdiagnosis and a prolonged diagnostic odyssey, ii) Family communication and dynamics surrounding health issues, iii) Perceptions of healthcare and one’s own health risks, and iv) The need for more intimate provider-patient relationships and communication. Overall, this study gleaned valuable insight from members of the Black community about possible factors contributing to the underdiagnosis of hATTR, as well as potential solutions to go about resolving this issue. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=cardiac%20amyloidosis" title="cardiac amyloidosis">cardiac amyloidosis</a>, <a href="https://publications.waset.org/abstracts/search?q=heart%20failure" title=" heart failure"> heart failure</a>, <a href="https://publications.waset.org/abstracts/search?q=TTR" title=" TTR"> TTR</a>, <a href="https://publications.waset.org/abstracts/search?q=genetic%20testing" title=" genetic testing"> genetic testing</a> </p> <a href="https://publications.waset.org/abstracts/145548/exploring-factors-that-may-contribute-to-the-underdiagnosis-of-hereditary-transthyretin-amyloidosis-in-african-american-patients" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/145548.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">98</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">1</span> MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAK Inhibitor-Naïve Myelofibrosis Patients</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Claire%20Harrison">Claire Harrison</a>, <a href="https://publications.waset.org/abstracts/search?q=Raajit%20K.%20Rampal"> Raajit K. Rampal</a>, <a href="https://publications.waset.org/abstracts/search?q=Vikas%20Gupta"> Vikas Gupta</a>, <a href="https://publications.waset.org/abstracts/search?q=Srdan%20Verstovsek"> Srdan Verstovsek</a>, <a href="https://publications.waset.org/abstracts/search?q=Moshe%20Talpaz"> Moshe Talpaz</a>, <a href="https://publications.waset.org/abstracts/search?q=Jean-Jacques%0D%0AKiladjian"> Jean-Jacques Kiladjian</a>, <a href="https://publications.waset.org/abstracts/search?q=Ruben%20Mesa"> Ruben Mesa</a>, <a href="https://publications.waset.org/abstracts/search?q=Andrew%20Kuykendall"> Andrew Kuykendall</a>, <a href="https://publications.waset.org/abstracts/search?q=Alessandro%20Vannucchi"> Alessandro Vannucchi</a>, <a href="https://publications.waset.org/abstracts/search?q=Francesca%20Palandri"> Francesca Palandri</a>, <a href="https://publications.waset.org/abstracts/search?q=Sebastian%0D%0AGrosicki"> Sebastian Grosicki</a>, <a href="https://publications.waset.org/abstracts/search?q=Timothy%20Devos"> Timothy Devos</a>, <a href="https://publications.waset.org/abstracts/search?q=Eric%20Jourdan"> Eric Jourdan</a>, <a href="https://publications.waset.org/abstracts/search?q=Marielle%20J.%20Wondergem"> Marielle J. Wondergem</a>, <a href="https://publications.waset.org/abstracts/search?q=Haifa%20Kathrin%20Al-Ali"> Haifa Kathrin Al-Ali</a>, <a href="https://publications.waset.org/abstracts/search?q=Veronika%0D%0ABuxhofer-Ausch"> Veronika Buxhofer-Ausch</a>, <a href="https://publications.waset.org/abstracts/search?q=Alberto%20Alvarez-Larr%C3%A1n"> Alberto Alvarez-Larrán</a>, <a href="https://publications.waset.org/abstracts/search?q=Sanjay%20Akhani"> Sanjay Akhani</a>, <a href="https://publications.waset.org/abstracts/search?q=Rafael%20Mu%C3%B1oz-Carerras"> Rafael Muñoz-Carerras</a>, <a href="https://publications.waset.org/abstracts/search?q=Yury%20Sheykin"> Yury Sheykin</a>, <a href="https://publications.waset.org/abstracts/search?q=Gozde%20Colak"> Gozde Colak</a>, <a href="https://publications.waset.org/abstracts/search?q=Morgan%20Harris"> Morgan Harris</a>, <a href="https://publications.waset.org/abstracts/search?q=John%20Mascarenhas"> John Mascarenhas</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=CPI-0610" title="CPI-0610">CPI-0610</a>, <a href="https://publications.waset.org/abstracts/search?q=JAKi%20treatment-na%C3%AFve" title=" JAKi treatment-naïve"> JAKi treatment-naïve</a>, <a href="https://publications.waset.org/abstracts/search?q=MANIFEST-2" title=" MANIFEST-2"> MANIFEST-2</a>, <a href="https://publications.waset.org/abstracts/search?q=myelofibrosis" title=" myelofibrosis"> myelofibrosis</a>, <a href="https://publications.waset.org/abstracts/search?q=pelabresib" title=" pelabresib"> pelabresib</a> </p> <a href="https://publications.waset.org/abstracts/148353/manifest-2-a-global-phase-3-randomized-double-blind-active-control-study-of-pelabresib-cpi-0610-and-ruxolitinib-vs-placebo-and-ruxolitinib-in-jak-inhibitor-naive-myelofibrosis-patients" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/148353.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">201</span> </span> </div> </div> <ul class="pagination"> <li class="page-item"><a class="page-link" href="https://publications.waset.org/abstracts/search?q=Calmodulin%20gene&page=50" rel="prev">&lsaquo;</a></li> <li class="page-item"><a class="page-link" href="https://publications.waset.org/abstracts/search?q=Calmodulin%20gene&page=1">1</a></li> <li class="page-item"><a class="page-link" href="https://publications.waset.org/abstracts/search?q=Calmodulin%20gene&page=2">2</a></li> <li class="page-item disabled"><span class="page-link">...</span></li> <li class="page-item"><a class="page-link" href="https://publications.waset.org/abstracts/search?q=Calmodulin%20gene&page=42">42</a></li> <li class="page-item"><a class="page-link" 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