Search results for: regional expression

Authors: Ngoc-Hieu Vu

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Although dairy production in Vietnam is a relatively new agricultural activity, milk production increased remarkably in recent years. Smallholders are still the main drivers for this development, especially in the southern part of the country. However, information on the farming practices is very limited. Therefore, this study aimed to characterize husbandry practices, educational experiences, decision-making practices, constraints, income and expenses of smallholder dairy farms in Southern Vietnam. A total of 200 farms, located in the regions Ho Chi Minh (HCM, N=80 farms), Lam Dong (N=40 farms), Binh Duong (N=40 farms) and Long An (N=40 farms) were included. Between October 2013 and December 2014 farmers were interviewed twice. On average, farms owned 3.200m2, 2.000m2, and 193m2 of pasture, cropping and housing area, respectively. The number of total, milking and dry cows, heifers, and calves were 20.4, 11.6, 4.7, 3.3, and 2.9 head. The number of lactating dairy cows was higher (p<0.001) in HCM (15.5) and Lam Dong (14.7) than in Binh Duong (6.7) and Long An (10.7). Animals were mainly crossbred Holstein-Friesian (HF) cows with at least 75% HF origin (84%), whereas a higher (P<0.001) percentage of purebred HF was found in HCM and Lam Dong and crossbreds in Binh Duong and Long An. Animals were mainly raised in tie-stalls (94%) and machine-milked (80%). Farmers used their own replacement animals (76%), and both genetic and phenotypic information (67%) for selecting sires. Farmers were predominantly educated at primary school level (53%). Major constraints for dairy farming were the lack of capital (43%), diseases (17%), marketing (22%), lack of knowledge (8%) and feed (7%). Monthly profit per lactating cow was superior in Lam Dong (2,817 thousand VND) and HCM (2,798 thousand VND) compared to other regions in Long An (2,597 thousand VND), and Binh Duong (1,775 thousand VND). Regional differences may be mainly attributed to environmental factors, urbanization, and particularly governmental support and the availability of extension and financial institutions. Results from this study provide important information on farming practices of smallholders in Southern Vietnam that are useful in determining regions that need to be addressed by authorities in order to improve dairy production.

Keywords: dairy farms, milk yield, Southern Vietnam, socio-economics

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Authors: Daniel Aberdam

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Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia-related keratopathy (ARK), caused by a combination of factors including limbal stem-cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub-epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation found in patients into one allele of the PAX6 gene into limbal stem cells. Resulting mutated clones, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency were further characterized. Sequencing analysis showed that no off-target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of soluble recombinant PAX6 protein into the culture medium was sufficient to activate endogenous PAX6 gene and, as a consequence, rescue the phenotype. It strongly suggests that our in vitro model recapitulates well the epithelial defect and becomes a powerful tool to identify drugs that could rescue the corneal defect in patients. Furthermore, we demonstrate that the homeotic transcription factor Pax6 is able to be uptake naturally by recipient cells to function into the nucleus.

Keywords: Pax6, crispr/cas9, limbal stem cells, aniridia, gene therapy

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Authors: Mohammad Hossein Habibi, Atena Sadat Hosseini

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Colorectal cancer is the third leading cause of cancer-related death in the world. Colorectal cancer screening, early detection, and treatment programs could benefit from the most up-to-date information on the disease's burden, given the present worldwide trend of increasing colorectal cancer incidence. Tumor recurrence and resistance are exacerbated by the presence of chemotherapy-resistant cancer stem cells that can generate rapidly proliferating tumor cells. In addition, tumor cells can evolve chemoresistance through adaptation mechanisms. In this work, we used in silico analysis to select suitable GEO datasets. In this study, we compared slow-growing cancer stem cells with high-growth colorectal cancer-derived cancer stem cells. We then evaluated the signal pathways, transcription factors, and kinases associated with these two types of cancer stem cells. A total of 980 upregulated genes and 870 downregulated genes were clustered. MAPK signaling pathway, AGE-RAGE signaling pathway in diabetic complications, Fc gamma R-mediated phagocytosis, and Steroid biosynthesis signaling pathways were observed in upregulated genes. Also, caffeine metabolism, amino sugar and nucleotide sugar metabolism, TNF signaling pathway, and cytosolic DNA-sensing pathway were involved in downregulated genes. In the next step, we evaluated the best transcription factors and kinases in two types of cancer stem cells. In this regard, NR2F2, ZEB2, HEY1, and HDGF as transcription factors and PRDM5, SMAD, CBP, and KDM2B as critical kinases in upregulated genes. On the other hand, IRF1, SPDEF, NCOA1, and STAT1 transcription factors and CTNNB1 and CDH7 kinases were regulated low expression genes. Using bioinformatics analysis in the present study, we conducted an in-depth study of colorectal cancer stem cells at low and high growth rates so that we could take further steps to detect and even target these cells. Naturally, more additional tests are needed in this direction.

Keywords: colorectal cancer, bioinformatics analysis, transcription factor, kinases, cancer stem cells

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Authors: Arditya Nugraha, Herry Gunawan, Agung P. Widodo

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The various possible strategies to find hydrocarbon are explored within a wide ranging of efforts. It started to identify petroleum concept in the basin. The main objectives of this paper are to integrate and develop information, knowledge, and evaluation from Indonesia’s sedimentary basins system in terms of their suitability for exploration activity and estimate the hydrocarbon potential available. The system which compiled data information and knowledge and comprised exploration and production data of all basins in Indonesia called as Basin Professor which stands for Basin Professional and Processor. Basin Professor is a website application using Geography Information System which consists of all information about basin montage, basin summary, petroleum system, stratigraphy, development play, risk factor, exploration history, working area, regional cross section, well correlation, prospect & lead inventory and infrastructure spatial. From 82 identified sedimentary basins, North Sumatra, Central Sumatra, South Sumatera, East Java, Kutai, and Tarakan basins are respectively positioned of the Indonesia’ s mature basin and the most productive basin. The Eastern of Indonesia also have many hydrocarbon potential and discovered several fields in Papua and East Abadi. Basin Professor compiled the well data in all of the basin in Indonesia from mature basin to frontier basin. Well known geological data, subsurface mapping, prospect and lead, resources and established infrastructures are the main factors make these basins have higher suitability beside another potential basin. The hydrocarbon potential resulted from this paper based on the degree of geological data, petroleum, and economic evaluation. Basin Professor has provided by a calculator tool in lead and prospect for estimate the hydrocarbon reserves, recoverable in place and geological risk. Furthermore, the calculator also defines the preliminary economic evaluation such as investment, POT IRR and infrastructures in each basin. From this Basin Professor, petroleum companies are able to estimate that Indonesia has a huge potential of hydrocarbon oil and gas reservoirs and still interesting for hydrocarbon exploration and production activity.

Keywords: basin summary, petroleum system, resources, economic evaluation

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Authors: Li Yang, Yang Song, Martin Y. M. Chiang

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Objective: To experimentally substantiate the micromechanical compatibility between cell and scaffold, in the regenerative medicine approach for restoring bone volume, is essential for phenotypic transitions Methods: Through nanotechnology and electrospinning process, nanofibrous scaffolds were fabricated to host dental follicle stem cells (DFSCs). Blends (50:50) of polycaprolactone (PCL) and silk fibroin (SF), mixed with various content of cellulose nanocrystals (CNC, up to 5% in weight), were electrospun to prepare nanofibrous scaffolds with heterogeneous microstructure in terms of fiber size. Colloidal probe atomic force microscopy (AFM) and conventional uniaxial tensile tests measured the scaffold stiffness at the micro-and macro-scale, respectively. The cell elastic modulus and cell-scaffold adhesive interaction (i.e., a chemical function) were examined through single-cell force spectroscopy using AFM. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine if the mechanotransduction signal (i.e., Yap1, Wwr2, Rac1, MAPK8, Ptk2 and Wnt5a) is upregulated by the scaffold stiffness at the micro-scale (cellular scale). Results: The presence of CNC produces fibrous scaffolds with a bimodal distribution of fiber diameter. This structural heterogeneity, which is CNC-composition dependent, remarkably modulates the mechanical functionality of scaffolds at microscale and macroscale simultaneously, but not the chemical functionality (i.e., only a single material property is varied). In in vitro tests, the osteogenic differentiation and gene expression associated with mechano-sensitive cell markers correlate to the degree of micromechanical compatibility between DFSCs and the scaffold. Conclusion: Cells require compliant scaffolds to encourage energetically favorable interactions for mechanotransduction, which are converted into changes in cellular biochemistry to direct the phenotypic evolution. The micromechanical compatibility is indeed important to the efficacy of regenerative medicine.

Keywords: phenotype transition, scaffold stiffness, electrospinning, cellulose nanocrystals, single-cell force spectroscopy

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Authors: Kamsiah Jaarin, Yusof Kamisah, Faizah Othman Nurul Akmal Muhammad, Zakiah Jubri, Qodriyah Mohd Saad, Srijit Das

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Forty (40) normotensive adult male Sprague-Dawley rats aged three months weighing 180-200 g were divided into 4 groups with 10 rats per group: (1) normotensive control; (2) hypertensive rats; (3) hypertensive rats treated with Nigella sativa (2.5 ml/kg/day); and (4) hypertensive rats treated with nicardipine (5 mg/kg/day). After acclimatization, the hypertensive rats of the group 2, 3 and 4 were induced to be hypertensive by giving NW–nitro-L-arginine methyl ester (L-NAME; 30 mg/kg/day) in their drinking water for consecutive 7 days. After one week, rats in the group 3 were given a daily oral dose of 2.5 ml/kg/day of Nigella sativa (NS) by oral gavage. Rats in the group 4 were given nicardipine (5 mg/kg/day) via oral gavages. All rats in this study received L-NAME continuously throughout the treatment duration. The blood pressure will be measured pre-treatment and weekly for 8 weeks using power lab. Blood was taken before and at the end of study for measurement of nitric oxide. At the end of 8 weeks, the rats are sacrificed and descending thoracic aorta was disserted for measurement of vascular reactivity, and intracellular adhesion molecules (ICAM-1) and vascular cell adhesion molecules (VCAM-1). Nigella sativa reduced both systolic and diastolic BP compared to control and L-name group. The BP lowering effect of NS was comparable to nicardipine a calcium antagonist. The blood pressure lowering effect of NS was accompanied with an increasing relaxation response to nitroprusside and acetylcholine and reducing vasoconstriction response to epinephrine. L-NAME and nicardipine on the other hand, reduced plasma nitric oxide concentration. In contrast, NS increased NO concentration. However, Nigella sativa had no significant effect on aortic VCAM- 1 and ICAM-1 expression. In conclusion; Nigella sativa oil reduces both systolic and diastolic blood pressure in L-NAME treated rats. The antihypertensive effect of NS was comparable to nicardipine. The BP lowering effect may be mediated via stimulating nitric oxide release from vascular endothelium.

Keywords: Nigella sativa, ICAM, VCAM, blood pressure, vascular reactivity

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Authors: Mahdi Sepehrmanesh

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This essay explores Gerald Vizenor's innovative concepts of the tragedy of absence and the comedy of presence as frameworks for understanding and challenging dominant narratives about Native American identity and history. Vizenor's work critiques the notion of irrevocable cultural loss and rigid definitions of Indigenous identity based on blood quantum and stereotypical practices. Through subversive humor, trickster figures, and storytelling, Vizenor asserts the active presence and continuance of Native peoples, advocating for a dynamic, self-determined understanding of Native identity. The essay examines Vizenor's use of postmodern techniques, including his engagement with simulation and hyperreality, to disrupt colonial discourses and create new spaces for Indigenous expression. It explores the concept of "crossblood" identities as a means of resisting essentialist notions of Native authenticity and embracing the complexities of contemporary Indigenous experiences. Vizenor's ideas of survivance and transmotion are analyzed as strategies for cultural resilience and adaptation in the face of ongoing colonial pressures. The interplay between absence and presence in Vizenor's work is discussed, particularly through the lens of shadow survivance and the power of storytelling. The essay also delves into Vizenor's critique of terminal creed and his promotion of natural reason as an alternative epistemology to Western rationalism. While acknowledging the significant influence of Vizenor's work on Native American literature and theory, the essay also addresses critiques of his approach, including concerns about the accessibility of his writing and its political effectiveness. Despite these debates, the essay argues that Vizenor's concepts offer a powerful vision of Indigenous futurity that is rooted in tradition yet open to change, inspiring hope and agency in the face of oppression. By examining Vizenor's multifaceted approach to Native American identity and presence, this essay contributes to ongoing discussions about Indigenous representation, cultural continuity, and resistance to colonial narratives in literature and beyond.

Keywords: gerald vizenor, identity native american literature, survivance, trickster discourse, identity

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Authors: Salma A. El-Marasy, Rehab F. Abdel-Rahman, Reham M. Abd-Elsalam

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The burden of stroke is intensely increasing worldwide. Brain injury following transient or permanent focal cerebral ischemia develops ischemic stroke as a consequence of a complex series of pathophysiological events. The aim of this study is to evaluate the possible neuroprotective effect of a dipeptidyl peptidase-4 inhibitor, vildagliptin, independent on its insulinotropic properties in non-diabetic rats subjected to cerebral ischemia. Anaesthetized Wistar rats were subjected to either left middle cerebral artery occlusion (MCAO) or sham operation followed by reperfusion after 30 min of MCAO. The other three groups were orally administered vildagliptin at 3 dose levels (2.5, 5, 10 mg/kg) for 3 successive weeks before subjected to left focal cerebral ischemia/reperfusion and till the end of the study. Neurological deficit scores and motor activity were assessed 24h following reperfusion. 48h following reperfusion, rats were euthanized and their left brain hemispheres were harvested and used in the biochemical, histopathological, and immunohistochemical investigations. Vildagliptin pretreatment improved neurological score deficit, locomotor activity and motor coordination in MCAO rats. Moreover, vildagliptin reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), phosphotylinosital 3 kinase (PI3K), phosphorylated of protein kinase B (p-AKT), and mechanistic target of rapamycin (mTOR) brain contents in addition to reducing protein expression of caspase-3. Also, vildagliptin showed a dose-dependent attenuation in neuronal cell loss and histopathological alterations in MCAO rats. This study proves that vildagliptin exerted the neuroprotective effect in a dose-dependent manner as shown in amelioration of neuronal cell loss and histopathological damage in MCAO rats, which may be mediated by attenuating neuronal and motor deficits, it’s anti-oxidant property, activation of PI3K/AKT/mTOR pathway and its anti-apoptotic effect.

Keywords: caspase-3, cerebral ischemia, dipeptidyl peptidase-4 inhibitor, oxidative stress, PI3K/AKT/mTOR pathway, rats, vildagliptin

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Authors: Zhao Xinlei

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In general, interstate relations are diverse and include economic, political, military, and diplomatic. Therefore, by analyzing the development of the relationship between Malaysia and China, we can better verify how the Hirschman effect works between small countries and great powers. This paper mainly adopts qualitative research methods and uses Malaysia's 2020-2022 political crisis as a specific case to verify the practice of the Hirschman effect between small and large countries. In particular, the interest groups in small countries that are closely related to trade with extraordinary abilities, as the primary beneficiaries in the development of trade between the two countries, although they may use their resources to a certain extent to influence the decisions of small countries towards great powers, they do not fundamentally determine the small countries' response to large countries. In this process, the relative power asymmetry between states plays a dominant role, as small states lack trust and suspicion in political diplomacy towards large states based on the perception of threat arising from the relative power asymmetry. When developing bilateral relations with large countries, small states seek practical cooperation to promote economic and trade development but become more cautious in their political ties to avoid being caught in power struggles between large states or being controlled by them. The case of Malaysia-China relations also illustrates that despite the ongoing political crisis in Malaysia, which saw the country go through the transition from (Perikatan Nasional) PN to (Barisan Nasional) BN, different governments have maintained a pragmatic and proactive economic policy towards China to reduce suspicion and mistrust between the two countries in political and diplomatic affairs, thereby enhancing cooperation and interactions between the two countries. At the same time, the Malaysian government is developing multi-dimensional foreign relations and actively participating in multilateral, regional organizations and platforms, such as those organized by the United States, to maintain a relative balance in the influence of the US and China on Malaysia.

Keywords: Hirschman effect, interest groups, Malaysia, China, bilateral relations

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Authors: Wojciech Górecki, Anna Sowiżdżał, Grzegorz Machowski, Tomasz Maćkowski, Bartosz Papiernik, Michał Stefaniuk

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The article shows results of the project which aims at evaluating possibilities of effective development and exploitation of natural gas from argillaceous series of the Autochthonous Miocene in the Carpathian Foredeep. To achieve the objective, the research team develop a world-trend based but unique methodology of processing and interpretation, adjusted to data, local variations and petroleum characteristics of the area. In order to determine the zones in which maximum volumes of hydrocarbons might have been generated and preserved as shale gas reservoirs, as well as to identify the most preferable well sites where largest gas accumulations are anticipated a number of task were accomplished. Evaluation of petrophysical properties and hydrocarbon saturation of the Miocene complex is based on laboratory measurements as well as interpretation of well-logs and archival data. The studies apply mercury porosimetry (MICP), micro CT and nuclear magnetic resonance imaging (using the Rock Core Analyzer). For prospective location (e.g. central part of Carpathian Foredeep – Brzesko-Wojnicz area) reprocessing and reinterpretation of detailed seismic survey data with the use of integrated geophysical investigations has been made. Construction of quantitative, structural and parametric models for selected areas of the Carpathian Foredeep is performed on the basis of integrated, detailed 3D computer models. Modeling are carried on with the Schlumberger’s Petrel software. Finally, prospective zones are spatially contoured in a form of regional 3D grid, which will be framework for generation modelling and comprehensive parametric mapping, allowing for spatial identification of the most prospective zones of unconventional gas accumulation in the Carpathian Foredeep. Preliminary results of research works indicate a potentially prospective area for occurrence of unconventional gas accumulations in the Polish part of Carpathian Foredeep.

Keywords: autochthonous Miocene, Carpathian foredeep, Poland, shale gas

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Authors: Tugce Duygu Koksal

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In recent years, given the fact that the acts of terrorism and the threat of the latter are taking place without any border and distinction, it has led the states to deal with the terrorism as a priority issue. More recently, as seen in different countries during state of emergency, the adoption of anti-terrorism measures motivated by the sole need of the prevention of terrorism targets directly the fundamental rights of individuals. Therefore, a contribution to the understanding of the value of the principle of legality is becoming more and more important nowadays. This paper aims to reflect the probable effects of the adoption of anti-terrorism measures regardless of the principle of legality, on the fundamental rights. In this respect, this paper will first discuss the margin of appreciation of the national authorities by countering terrorism, and then, the importance of the respect of the legality of the anti-terrorism measures will be examined in the light of actual examples. Indeed, one of the major findings of this study is the fact that the anti-terrorism laws and measures were taken in this framework must be subject to close scrutiny in democracies, which adopted the principle of the rule of law and respect human rights. Although the state's margin of appreciation in the field of counter-terrorism is broad, these measures which are based on the legitimate aim of a democracies’ legitimate right to protect itself against the activities of terrorist organizations should have the legal basis and be strictly required by the exigencies of the fight against terrorism. While combating terrorism, the legal basis shall only be achieved if the legal consequences of an individuals’ actions related to terrorism shall be clear and foreseeable by the individuals of a society. On the other hand, particularly during the state of emergency, the ambiguity of the law might be used to include a wide range of actions under acts of terrorism. This is becoming more dangerous where freedom of expression, freedom of the press, freedom of association and the right to information is in the substance of these actions. Disregarding the principle of legality is susceptible to create a chilling effect on the exercise of human rights, and therefore, the fight against terrorism can be transformed into a repressive regime on opponents. As a result, the efforts to counter terrorism of the national authorities irrespective of the principle of legality are susceptible to cause a transformation of the rule of law to a state of law which cannot be appreciated in a democratic society.

Keywords: anti-terrorism measures, chilling effect, predictability, the principle of legality, state of emergency

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Authors: Safee Chaudhary, Mahnoor Naseer Gondal, Hira Anees Awan, Abdul Rehman, Ammar Arif, Risham Hussain, Huma Khawar, Zainab Arshad, Muhammad Faizyab Ali Chaudhary, Waleed Ahmed, Muhammad Umer Sultan, Bibi Amina, Salaar Khan, Muhammad Moaz Ahmad, Osama Shiraz Shah, Hadia Hameed, Muhammad Farooq Ahmad Butt, Muhammad Ahmad, Sameer Ahmed, Fayyaz Ahmed, Omer Ishaq, Waqar Nabi, Wim Vanderbauwhede, Bilal Wajid, Huma Shehwana, Muhammad Tariq, Amir Faisal

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Cancer is a manifestation of multifactorial deregulations in biomolecular pathways. These deregulations arise from the complex multi-scale interplay between cellular and extracellular factors. Such multifactorial aberrations at gene, protein, and extracellular scales need to be investigated systematically towards decoding the underlying mechanisms and orchestrating therapeutic interventions for patient treatment. In this work, we propose ‘TISON’, a next-generation web-based multiscale modeling platform for clinical systems oncology. TISON’s unique modeling abstraction allows a seamless coupling of information from biomolecular networks, cell decision circuits, extra-cellular environments, and tissue geometries. The platform can undertake multiscale sensitivity analysis towards in silico biomarker identification and drug evaluation on cellular phenotypes in user-defined tissue geometries. Furthermore, integration of cancer expression databases such as The Cancer Genome Atlas (TCGA) and Human Proteome Atlas (HPA) facilitates in the development of personalized therapeutics. TISON is the next-evolution of multiscale cancer modeling and simulation platforms and provides a ‘zero-code’ model development, simulation, and analysis environment for application in clinical settings.

Keywords: systems oncology, cancer systems biology, cancer therapeutics, personalized therapeutics, cancer modelling

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Authors: Patricia Portugal Marques de Carvalho Lourenco

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A three-phase methodological multi-lingual path was designed, constructed and carried out using the 2020 Chinese Internet Drama Series We Are All Alone as a case study. Phase one, the backbone of the research, comprised of secondary data analysis, providing the structure on which the next two phases would be built on. Phase one incorporated a Google Scholar and a Baidu Index analysis, Star Network Influence Index and Mydramalist.com top two drama reviews, along with an article written about the drama and scrutiny of Chinese related blogs and websites. Phase two was field research elaborated across Latin Europe, and phase three was social media focused, having into account that perceptions are going to be memory conditioned based on past ideas recall. Overall, research has shown the poor cultural expression of Chinese entertainment in Latin Europe and demonstrated the inexistence of Chinese content in French, Italian, Portuguese and Spanish Business to Consumer retailers; a reflection of their low significance in Latin European markets and the short-life cycle of entertainment products in general, bubble-gum, disposable goods without a mid to long-term effect in consumers lives. The process of conducting comprehensive international research was complex and time-consuming, with data not always available in Mandarin, the researcher’s linguistic deficiency, limited Chinese Cultural Knowledge and cultural equivalence. Despite steps being taken to minimize the international proposed research, theoretical limitations concurrent to Latin Europe and China still occurred. Data accuracy was disputable; sampling, data collection/analysis methods are heterogeneous; ascertaining data requirements and the method of analysis to achieve a construct equivalence was challenging and morose to operationalize. Secondary data was also not often readily available in Mandarin; yet, in spite of the array of limitations, research was done, and results were produced.

Keywords: research methodologies, international research, primary data, secondary data, research limitations, online dramas, china, latin europe

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Authors: Muhammad Naeem, Juho Lee, Jin-Wook Yoo

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In this study, we hypothesized that prolonged gastrointestinal transit at the inflamed colon conferred by a pH-triggered mucoadhesive smart nanoparticulate drug delivery system aids in achieving selective and sustained levels of the drug within the inflamed colon for the treatment of ulcerative colitis. We developed budesonide-loaded pH-sensitive charge-reversal solid lipid nanoparticles (SLNs) using a hot homogenization method. Polyetylenimine (PEI) was used to render SLNs cationic (PEI-SLNs). Eudragit S100 (ES) was coated on PEI-SLNs for pH-trigger charge-reversal SLNs (ES-PEI-SLNs). Therapeutic potential of the prepared SNLs formulation was evaluated in ulcerative colitis in mice. The transmission electron microscopy, zeta size and zeta potential data showed the successful formation of SLNs formulations. SLNs and PEI-SLNs showed burst drug release in acidic pH condition mimicking stomach and early small intestine environment which limiting their application as oral delivery systems. However, ES-PEI-SLNs prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. Most importantly, the surface charge of ES-PEI-SLNs switched from negative to positive in colonic conditions by pH-triggered removal of ES coating and accumulated selectively in inflamed colon. Furthermore, a charge reversal ES-PEI-SLNs showed a superior mitigation of dextran sulfate sodium (DSS)-induced acute colitis in mice as compared to SLNs and PEI-SLNs treated groups. Moreover, histopathological analysis of distal colon sections stained with hematoxylin/eosin and E-cadherin immunostaining revealed attenuated inflammation in an ES-PEI-SLNs-treated group. We also found that ES-PEI-SLNs markedly reduced the myeloperoxidase level and expression of TNF-alpha in colon tissue. Our results suggest that the pH-triggered charge reversal SLNs presented in this study would be a promising approach for ulcerative colitis therapy.

Keywords: solid lipid nanoparticles, stimuli-triggered charge-reversal, ulcerative colitis, methacrylate copolymer, budesonide

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Authors: Zelalem B. Gurmessa, Ignatius W. Ferreira, Henry F. Wissink

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The aim of this paper is to critically examine the factors contributing to academic brain drain in the Sub-Saharan Africa with specific reference to the higher education sector. Africa in general and Sub-Saharan African (SSA) countries, in particular, are experiencing an exodus of highly trained, qualified and competent human resources to other developing and developed countries thereby threatening the overall development of the relevant regions and impeding both public and private service delivery systems in the nation states. The region is currently in a dire situation in terms of health care services, education, science, and technology. The contribution of SSA countries to Science, Technology and Innovation is relatively minimal owing to the migration of skilled professionals due to both push and pull factors. The phenomenon calls for both international and trans-boundary, regional, national and institutional interventions to curb the exodus. Based on secondary data and the review of the literature, the article conceptualizes the antecedents and impacts of human capital flight or brain drain in the SSA countries from a higher education perspective. To this end, the article explores the magnitude, causes, and impacts of brain drain in the region. Despite the lack of consistent data on the magnitude of academic brain drain in the region, a critical analysis of the existing sources shows that pay disparity between developing and developed countries, the lack of enabling working conditions at source countries, fear of security due to political turmoil or unrest, the availability of green pastures and opportunity for development in the receiving countries were identified as major factors contributing to academic brain drain in the region. This hampers the socio-economic, technological and political development of the region. The paper also recommends that further research can be undertaken on the magnitude, causes, characteristics and impact of brain drain on the sustainability and competitiveness of SSA higher education institutions in the region.

Keywords: brain drain, higher education, sub-Saharan Africa, sustainable development

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Authors: Luiz Nolasco Jr. Rezende, Antonio Villar M. Sá, Claudia Marcia L. Pato

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The increasing urban violence in Brazil involves more and more infractions committed by children and youths. The challenges faced by the institutional environments responsible for the education and resocialization of adolescents in conflict with the law are enormous, especially of those deprived of their liberty. These institutions have an inadequate educational structure. They are characterized by a dirty and unhealthy environment without the minimum basic conditions for their activities, by frequent practices of degradation, humiliation, and the physical and psychological punishment of inmates. This mixed-method study investigated the personal values of adolescents with restriction of freedom in a socio-educational institutional environment aiming to contribute to the development of their morality through an educational process. For that, we used a survey and transdisciplinary play workshops involving thirty-two boys aged between 15 and 19 years old and at least two years out of school. To evaluate the survey the reduced version of the Portrait Questionnaire—PQ21—was used. The workshops happened once a week, lasting 80 minutes each, totaling twelve meetings. By using the game of chess and its metaphors, participants produced texts and engaged in critical brainstorming about their lives. The survey results pointed out that these young people showed a predominance of values of openness to change and self-transcendence, dissatisfaction with one's own reality and surroundings, not considering the consequences of their actions on themselves and others, difficulties in speaking and writing, and desire for changes in their lives. After the pedagogical interventions, these adolescents demonstrated an understanding of the implications of their actions for themselves, for their families, especially for the mothers, with whom they demonstrated stronger bonds. It was possible to observe evidence of improvement in the capacity of linguistic expression, more autonomy and critical vision, including about themselves and their respective contexts. These results demonstrated the educational potential of lively, symbolic, dynamic and playful activities that favor the mediation and identification of these adolescents with their lives, and contribute to the projection of dreams.

Keywords: adolescents arrested, human values, moral development, playful workshops

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Authors: Achitphol Chookaew, Paramee Thongsukhsai, Patamarerk Engsontia, Narongwit Nakwan, Pritsana Raugrut

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Lung cancer is one of the most common malignancies and primary cause of death due to cancer worldwide. Non-small cell lung cancer (NSCLC) is the main subtype in which majority of patients present with advanced-stage disease. Herein, we analyzed differentially expressed genes to find potential biomarkers for lung cancer diagnosis as well as prognostic markers. We used transcriptome data from our 2 NSCLC patients and public data (GSE81089) composing of 8 NSCLC and 10 normal lung tissues. Differentially expressed genes (DEGs) between NSCLC and normal tissue and between early-stage and late-stage NSCLC were analyzed by the DESeq2. Pairwise correlation was used to find the DEGs with false discovery rate (FDR) adjusted p-value £ 0.05 and |log2 fold change| ³ 4 for NSCLC versus normal and FDR adjusted p-value £ 0.05 with |log2 fold change| ³ 2 for early versus late-stage NSCLC. Bioinformatic tools were used for functional and pathway analysis. Moreover, the top ten genes in each comparison group were verified the expression and survival analysis via GEPIA. We found 150 up-regulated and 45 down-regulated genes in NSCLC compared to normal tissues. Many immnunoglobulin-related genes e.g., IGHV4-4, IGHV5-10-1, IGHV4-31, IGHV4-61, and IGHV1-69D were significantly up-regulated. 22 genes were up-regulated, and five genes were down-regulated in late-stage compared to early-stage NSCLC. The top five DEGs genes were KRT6B, SPRR1A, KRT13, KRT6A and KRT5. Keratin 6B (KRT6B) was the most significantly increased gene in the late-stage NSCLC. From GEPIA analysis, we concluded that IGHV4-31 and IGKV1-9 might be used as diagnostic biomarkers, while KRT6B and KRT6A might be used as prognostic biomarkers. However, further clinical validation is needed.

Keywords: differentially expressed genes, early and late-stages, gene ontology, non-small cell lung cancer transcriptomics

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Authors: Hacer Kobya Bulut, Kıymet Yeşilçiçek Çalık, Birsel Canan Demirbağ, Hacer Erdöl, Songül Aktaş

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Introduction: As an expression of an emotion which always exists in life, crying is regarded as one of the problematic behaviors of patients by nurses. Towards such patients, nurses may exhibit emotional and behavioral reactions such as feeling helpless, anger, indifferent, defense, and opposition. However crying either meets a need, reduces the tension to cope with problems or helps patient to gain strength. Therefore, nurses must accept that crying is a normal mechanism that reduces emotional tension and should approach a crying patient accordingly. Objective: This study was carried out to evaluate the communicational behaviors of the nurses towards ‘crying patient’. Methods: This descriptive study was conducted with the nurses working at a university hospital in a city in the Eastern Black Sea in June-September 2015. The entire universe was tried to be reached without sampling. 90% of the population was reached and the study was completed with 309 nurses who volunteered to participate in the study. Data were collected through a questionnaire which was prepared reviewing the literature by researchers. Data were evaluated in SPSS analysis program using percentages, numbers and chi-square test with the 95% confidence interval and p <0.05significance level. Findings: The findings showed that the average age of nurses was 31.52 ± 7.96, work experience was 10:09 ± 7.69 and only 22.7% had training about ‘approach to crying patient’ during their education. 97.1% of the nurses often faced with crying patients in their professional lives, 62.8% stated that they faced crying women patients. When they see crying patients, 84.8% of the nurses ‘do not want the patient to cry’, 80.9% wonder ‘why they are crying’, % 79.6 ‘feel uneasiness’,% 79.3 ‘feel sorry’ and 41.4% ‘ feel helpless’. The question ‘Why do you think the patient is crying?’ was answered by 93.5% nurses as ‘they are suffering’, by 86.1% ‘they are helpless’, 80.9% ‘they are sad’, 79.6% ‘they need help’, 54.4% ‘because they feel inadequate,’ and 44.7% ‘they fail to control their crying behavior. ‘How do you approach to your patient when she/he is crying?’ question was answered by 82.5% of nurses as ‘I would console’, 77.3% as ‘I would ask the reason’, 63.1% as ‘I would try to stop her from crying’ all of which are actually inappropriate nursing approaches. However, 92.2% of the nurses stated that ‘I do not judge the crying patient’, ‘87.1% said ‘I allocate time to crying patients’ and 85.8% said ‘ I ask patient whether they want to cry alone’. The study showed that educational background and work experience of the nurses affected the appropriate approach to crying patients (P <0.05). Conclusion: As a result of the study, it was found out that nurses do not want patients to cry, so they exhibit inappropriate approach such as consoling the patients and they have difficulty in approaching crying patients.

Keywords: approach to patient, communication, crying patient, nurse, Turkey

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Authors: Shazia Shamim, Pallavi Gautam

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The present study describes the presence of rare or endangered plants from Poonch Dist., which spread over 1674 Km sq. located between latitude 330 25' N to 340 01' N and longitude 730 58' E to 740 35' E forming a part of the Northwest Himalaya in Jammu and Kashmir state of India, with the aim of suggesting the strategy for the conservation and promotion of cultivation of rare and endangered medicinal plants, as well as developing traditional knowledge of medicinal plants. The main threats to biodiversity and ecosystem are overexploitation, global climate change, habitat loss, fragmentation, pollution, and invasion of alien species and disturbance of community structure. Surveys were carried out during 2015-2016 throughout the Poonch valley. During the field survey, various criteria of International Union for the conservation of nature for categorizing threatened plants, extent of occurrence, area of occupancy, probability of extinction, etc. were measured. The rarity of species was determined by field study, visual estimations, and literature. During the collection, it was observed that few rare and endangered species which were present in the study area, are also mentioned in the prescribed red data book of Indian plants, International Union for conservation of nature, list of threatened species and list of Botanical Survey of India presented by its Northern Regional Centre. The study was based on extensive surveys of the study area and then concluded by preparing a list of plant species occurring in different seasons, the photographs of all these plant species were collected. Actual threats to the population of a selected plant species in a given area were recorded by direct observation. The present paper provides information about 22 rare and endangered medicinal plant species belonging to 18 families that are used by the native of these areas. Information provided includes botanical name, family name, local name, habitat, part used, ethno medicinal uses and brief preparation of the reported plant species is presented in the present work.

Keywords: biodiversity, traditional knowledge, International Union for Conservation of Nature, Botanical Survery of India

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Authors: S. Kozlovski, S.W. Feigelson, R. Alon

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The b2 integrin ligands ICAM-1 ICAM-2 and the endothelial VLA-4 integrin ligand VCAM-1 are constitutively expressed on different lung vessels and on high endothelial venules (HEVs), the main portal for lymphocyte entry from the blood into lung draining lymph nodes. ICAMs are also ubiquitously expressed by many antigen-presenting leukocytes and have been traditionally suggested as critical for the various antigen-specific immune synapses generated by these distinct leukocytes and specific naïve and effector T cells. Loss of both ICAM-1 and ICAM-2 on the lung vasculature reduces the ability to patrol monocytes and Tregs to patrol the lung vasculature at a steady state. Our new findings suggest, however, that in terms of innate leukocyte trafficking into the lung lamina propria, both constitutively expressed and virus-induced vascular VCAM-1 can functionally compensate for the loss of these ICAMs. In a mouse model for influenza infection, neutrophil and NK cell recruitment and clearance of influenza remained normal in mice deficient in both ICAMs. Strikingly, mice deficient in both ICAMs also mounted normal influenza-specific CD8 proliferation and differentiation. In addition, these mice normally combated secondary influenza infection, indicating that the presence of ICAMs on conventional dendritic cells (cDCs) that present viral antigens are not required for immune synapse formation between these APCs and naïve CD8 T cells as previously suggested. Furthermore, long-lasting humoral responses critical for protection from a secondary homosubtypic influenza infection were also normal in mice deficient in both ICAM-1 and ICAM-2. Collectively, our results suggest that the expression of ICAM-1 and ICAM-2 on lung endothelial and epithelial cells, as well as on DCs and B cells, is not critical for the generation of innate or adaptive anti-viral immunity in the lungs. Our findings also suggest that endothelial VCAM-1 can substitute for the functions of vascular ICAMs in leukocyte trafficking into various lung compartments.

Keywords: emigration, ICAM-1, lymph nodes, VCAM-1

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Authors: S. Junaid S. Qazi, Denice C. Bay, Raymond Chew, Raymond J. Turner

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EmrE, a member of the small multidrug resistance protein family in bacteria is considered to be the archetypical member of its family. It confers host resistance to a wide variety of quaternary cation compounds (QCCs) driven by proton motive force. Generally, purification yield is a challenge in all membrane proteins because of the difficulties in their expression, isolation and solubilization. EmrE is extremely hydrophobic which make the purification yield challenging. We have purified EmrE protein using two different approaches: organic solvent membrane extraction and hexahistidine (his6) tagged Ni-affinity chromatographic methods. We have characterized changes present between ligand affinity of untagged and his6-tagged EmrE proteins in similar membrane mimetic environments using biophysical experimental techniques. Purified proteins were solubilized in a buffer containing n-dodecyl-β-D-maltopyranoside (DDM) and the conformations in the proteins were explored in the presence of four QCCs, methyl viologen (MV), ethidium bromide (EB), cetylpyridinium chloride (CTP) and tetraphenyl phosphonium (TPP). SDS-Tricine PAGE and dynamic light scattering (DLS) analysis revealed that the addition of QCCs did not induce higher multimeric forms of either proteins at all QCC:EmrE molar ratios examined under the solubilization conditions applied. QCC binding curves obtained from the Trp fluorescence quenching spectra, gave the values of dissociation constant (Kd) and maximum specific one-site binding (Bmax). Lower Bmax values to QCCs for his6-tagged EmrE shows that the binding sites remained unoccupied. This lower saturation suggests that the his6-tagged versions provide a conformation that prevents saturated binding. Our data demonstrate that tagging an integral membrane protein can significantly influence the protein.

Keywords: small multidrug resistance (SMR) protein, EmrE, integral membrane protein folding, quaternary ammonium compounds (QAC), quaternary cation compounds (QCC), nickel affinity chromatography, hexahistidine (His6) tag

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Authors: Kristin Thooft

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— Increasing pressure to manage healthcare costs has resulted in shifting care towards ambulatory settings and is driving a focus on cost transparency. There are few nurse staffing to workload models developed for ambulatory settings, less for multi-specialty clinics. Of the existing models, few have been evaluated against outcomes to understand any impact. This evaluation took place after the AWARD model for nurse staffing to workload was implemented in a multi-specialty clinic at a regional healthcare system in the Midwest. The multi-specialty clinic houses 26 medical and surgical specialty practices. The AWARD model was implemented in two specialty practices in October 2020. Donabedian’s Structure-Process-Outcome (SPO) model was used to evaluate outcomes based on changes to the structure and processes of care provided. The AWARD model defined and quantified the processes, recommended changes in the structure of day-to-day nurse staffing. Cost of care per patient visit, total visits, a total nurse performed visits used as structural and process measures, influencing the outcomes of cost of care and access to care. Independent t-tests were used to compare the difference in variables pre-and post-implementation. The SPO model was useful as an evaluation tool, providing a simple framework that is understood by a diverse care team. No statistically significant changes in the cost of care, total visits, or nurse visits were observed, but there were differences. Cost of care increased and access to care decreased. Two weeks into the post-implementation period, the multi-specialty clinic paused all non-critical patient visits due to a second surge of the COVID-19 pandemic. Clinic nursing staff was re-allocated to support the inpatient areas. This negatively impacted the ability of the Nurse Manager to utilize the AWARD model to plan daily staffing fully. The SPO framework could be used for the ongoing assessment of nurse staffing performance. Additional variables could be measured, giving a complete picture of the impact of nurse staffing. Going forward, there must be a continued focus on the outcomes of care and the value of nursing

Keywords: ambulatory, clinic, evaluation, outcomes, staffing, staffing model, staffing to workload

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Authors: Rajendra Kumar Pandey

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Forest genetic resources not only represent regional biodiversity but also have immense value as the wealth for securing livelihood of poor people. These are vulnerable to ecological due to depletion/deforestation and /or impact of climate change. These resources of various plant categories are vulnerable on the floor of natural tropical forests, and leading to the threat on the growth and development of future forests. More than 170 species, including NTFPs, are in critical condition for their survival in natural tropical forests of Central India. Forest degradation, commensurate with biodiversity loss, is now pervasive, disproportionately affecting the rural poor who directly depend on forests for their subsistence. Looking ahead the interaction between forest and water, soil, precipitation, climate change, etc. and its impact on biodiversity of tropical forests, it is inevitable to develop co-operation policies and programmes to address new emerging realities. Forests ecosystem also known as the 'wealth of poor' providing goods and ecosystem services on a sustainable basis, are now recognized as a stepping stone to move poor people beyond subsistence. Poverty alleviation is the prime objective of the Millennium Development Goals (MDGs). However, environmental sustainability including other MDGs, is essential to ensure successful elimination of poverty and well being of human society. Loss and degradation of ecosystem are the most serious threats to achieving development goals worldwide. Millennium Ecosystem Assessment (MEA, 2005) was an attempt to identify provisioning and regulating cultural and supporting ecosystem services to provide livelihood security of human beings. Climate change may have a substantial impact on ecological structure and function of forests, provisioning, regulations and management of resources which can affect sustainable flow of ecosystem services. To overcome these limitations, policy guidelines with respect to planning and consistent research strategy need to be framed for conservation and sustainable development of forest genetic resources.

Keywords: climate change, forest ecosystem services, sustainable forest management, biodiversity conservation

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Authors: Kai Pai Huang

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Background: There are several types of plasma cell neoplasms including multiple myeloma, plasmacytoma, lymphoplasmacytic lymphoma, and monoclonal gammopathy of undetermined significance (MGUS) are found in our lab. Today, we want to compare with two cases using the method of capillary electrophoresis. Method: Serum is prepared and electrophoresis is performed at alkaline PH in a capillary using the Sebia® Capillary 2. Albumin and globulins are detected by the detector which is located in the cathode of the capillary and the signals are transformed to peaks. Serum was treated with beta-mercaptoethanol which reducing the polymerized immunoglobulin to monomer immunoglobulin to clarify two M-protein are secreted from the same plasma cell clone in bone marrow. Result: Case 1: A 78-year-old female presenting dysuria, oliguria and leg edema for several months. Laboratory data showed proteinuria, leukocytosis, results of high serum IgA and lambda light chain. A renal biopsy found amyloid fibrils in the glomerular mesangial area. Serum protein electrophoresis shows a major monoclonal peak in the β region and minor small peak in gamma region, and the immunotyping studies for serum showed two IgA/λ type. Case 2: A 55-year-old male presenting abdominal distension and low back pain for more than one month. Laboratory data showed T12 T8 compression fracture, results of high serum IgM and kappa light chain. Bone marrow aspiration showed the cells from the bone marrow are B cells with monotypic kappa chain expression. Bone marrow biopsy found this is lymphoplasmacytic lymphoma (Waldenstrom macroglobulin). Serum protein electrophoresis shows a monoclonal peak in the β region and the immunotyping studies for serum showed IgM/κ type. Conclusion: Plasma cell neoplasm can be diagnosed by many examinations. Among them, using capillary electrophoresis by a lab can separate several types of gammopathy and the quantification of a monoclonal peak can be used to evaluate the patients’ prognosis or treatment.

Keywords: plasma cell neoplasm, capillary electrophoresis, serum protein electrophoresis, immunotyping

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Authors: Nadia Naseem, Farwa Batool, Nasir Mehmood, AbdulHannan Nagi

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Background: The incidence and mortality of breast cancer vary significantly in geographically distinct populations. In Pakistan, breast cancer has shown an increase in incidence in young females and is characterized by more aggressive behavior. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. This study investigated the TP53 mutations in molecular subtypes of both nodes negative and positive breast cancer in young Pakistani patients. Material and Methods: p53, Estrogen Receptor (ER), Progesterone Receptor (PR), Her-2 neu and Ki 67 expressions were analyzed immunohistochemically in a series of 75 node negative (A) and 75 node positive (B) young (aged: 19-40 years) breast cancer patients diagnosed between 2014 to 2017 at two leading hospitals of Punjab, Pakistan. Tumor tissue specimens and peripheral blood samples were examined for TP53 mutations by direct sequencing of the gene (exons 4-9). The relation of TP53 mutations to these markers and clinicopathological data was investigated. Results: Mean age of the patients was 32.4 + 9.1 SD. Invasive breast carcinoma was the most frequent histological variant (A=92%, B=94.6%). Grade 3 carcinoma was the commonest grade (A=72%, B=81.3%). Triple negative cases (ER-, PR-, Her-2) formed most of the molecular subtypes (A=44%, B=50.6%). A total of 17.2% (A: 6.6%, B: 10.6%) patients showed TP53 mutations. Mutations were significantly more frequent in triple negative cases (A: 74.8%, B: 62.2%) compared to HER2-positive patients (P < 0.0001). In the multivariate analysis of the whole patient group, the independent prognosticator were triple negative cases (P=0.021), TP53 overexpression by IHC (P=0.001) and advanced-stage disease (P=0.007). No statistically significant correlation between TP53 mutations and clinicopathological parameters was found (P < 0.05). Conclusions: It is concluded that TP53 mutations are infrequently present in breast carcinoma of young Pakistani population and there was no significant correlation between p53 mutation and early onset disease. Immunohistochemically detected TP53 expression in our resource-constrained to set up can be beneficial in predicting mutations at the younger age in our population.

Keywords: immunohistochemistry (IHC), invasive breast carcinoma (IBC), Pakistan, TP53

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Authors: Mpho Mokoatle, Darlington Mapiye, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

Abstract:

Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on $k$-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0%, 80.5%, 80.5%, 63.6%, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms.

Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing

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Authors: Darlington Mapiye, Mpho Mokoatle, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

Abstract:

Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on k-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0 %, 80.5 %, 80.5 %, 63.6 %, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms

Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing

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Authors: Fatemeh Dehghan Khangahi, Hakan Gunes

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Transforming a public necessity into a commercial commodity becomes more and more evident as time goes on, and it is one of the issues of water shortage. Development projects of countries, consume the water and waterbeds in various forms, ignoring the concepts such as sustainability and the negative effects they place on the environment, pollute and change the ways of waterways. Throughout these processes, the water basins and all the vital environments sometimes can suffer damage to the irreparable level. In this context, the issue of Lake Urmia that is located in the North West of Iran left alone by drought, has been researched. The lake, which is on the list of UNESCO's biosphere reserves, is now exposed to the danger of desiccation. If the desiccation is fully realized, more than 5.000.000 people that they are living around the lake, will have to migrate as a result of negative living conditions. As a matter of fact, along with the recent years of increasing drought level, regional migrations have begun. In addition to migration issues, it is also necessary to specify the negative effects on human and all-round’s life that depend on the formation of salt storms, mixing of salt into the air and soil, which threaten human health seriously because the lake is salty. The main aim of this work is to raise national and international awareness of this problem, which is an environment and a human tragedy at the same time. This research has two basic questions: 1) In the case of Lake Urmia, what are environmental problems and how they have emerged and what is the role of governments? 2) What is the social consequence of this problem in relation to the first question? In response, after the literature search, having a comparative view of the situation of the Aral Sea and the Great Salt Lake (Utah, USA), which involved the two major international examples. The first, one is related to the terms of population and migration, the second is about biological properties. Then, data and status information that provided after 3 years area research has been evaluated. Towards the end, with the support of qualitative and quantitative methods, the study of social mobilization in the region has been carried out. An example of it is using the public space of TRAXTOR matches like a protests area.

Keywords: environment problems, water, social mobilization, Lake Urmia, migration

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Authors: Antonio Lopez-Villegas, Rafael Bautista-Mesa, Emilio Robles-Musso, Daniel Catalan-Matamoros, Cesar Leal-Costa

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Objectives: The purpose of this trial was to evaluate the burden borne by and the costs to informal caregivers of users with telemonitoring of pacemakers. Methods: This is a controlled, non-randomised clinical trial, with data collected from informal caregivers, five years after implantation of pacemakers. The Spanish version of the Survey on Disabilities, Personal Autonomy, and Dependency Situations was used to get information on clinical and social characteristics, levels of professionalism, duration and types of care, difficulties in providing care, health status, economic and job aspects, impact on the family or leisure due to informal caregiving for patients with pacemakers. Results: After five years of follow-up, 55 users with pacemakers finished the study. Of which, 50 were helped by a caregiver, 18 were included in the telemonitoring group (TM) and 32 in the conventional follow-up group (HM). Overall, females represented 96.0% of the informal caregivers (88.89% in TM and 100.0% in HM group). The mean ages were 63.17 ± 15.92 and 63.13 ± 14.56 years, respectively (p = 0.83) in the groups. The majority (88.0%) of the caregivers declared that they had to provide their services between 6 and 7 days per week (83.33% in TM group versus 90.63% in HM group), without significant differences between both groups. The costs related to care provided by the informal caregivers were 47.04% higher in the conventional follow-up group than in the TM group. Conclusions: The results of this trial confirm that there were no significant differences between the informal caregivers regarding to baseline characteristics, workload and time worked in both groups of follow-up. The costs incurred by the informal caregivers providing care for users with pacemakers included in telemonitoring group are significantly lower than those in the conventional follow-up group. Trial registration: ClinicalTrials.gov NCT02234245. Funding: The PONIENTE study, has been funded by the General Secretariat for Research, Development and Innovation, Regional Government of Andalusia (Spain), project reference number PI/0256/2017, under the research call 'Development and Innovation Projects in the Field of Biomedicine and Health Sciences', 2017.

Keywords: costs, disease burden, informal caregiving, pacemaker follow-up, remote monitoring, telemedicine

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Authors: Neha Toppo

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Method and strategies of teaching instruction highly influence learning of students. In second language teaching, number of ways and methods has been suggested by different scholars and researchers through times. The present article deals with the role of teaching instruction in developing compositional ability of students in writing. It focuses on the secondary level students of rural areas, whose exposure to English language is limited and they face challenges even in simple compositions. The students till high school suffer with their disability in writing formal letter, application, essay, paragraph etc. They face problem in note making, writing answers in examination using their own words and depend fully on rote learning. It becomes difficult for them to give language to their own ideas. Teaching writing composition deserves special attention as writing is an integral part of language learning and students at this level are expected to have sound compositional ability for it is useful in numerous domains. Effective method of instruction could help students to learn expression of self, correct selection of vocabulary and grammar, contextual writing, composition of formal and informal writing. It is not limited to school but continues to be important in various other fields outside the school such as in newspaper and magazine, official work, legislative work, material writing, academic writing, personal writing, etc. The study is based on the experimental method, which hypothesize that guided instruction will be more effective in teaching writing compositions than usual instruction in which students are left to compose by their own without any help. In the test, students of one section are asked to write an essay on the given topic without guidance and another section are asked to write the same but with the assistance of guided instruction in which students have been provided with a few vocabulary and sentence structure. This process is repeated in few more schools to get generalize data. The study shows the difference on students’ performance using both the instructions; guided and unguided. The conclusion of the study is followed by the finding that writing skill of the students is quite poor but with the help of guided instruction they perform better. The students are in need of better teaching instruction to develop their writing skills.

Keywords: composition, essay, guided instruction, writing skill

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