Search results for: sequential causal inference

Authors: Mona Vijayaran, Gurleen Oberoi, Sanjay Mishra

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Introduction: p190 BCR‐ABL1 in CML is often associated with monocytosis. In the case described here, monocytosis is associated with coexisting p210 BCR‐ABL and CMML clones. Mutation analysis using next‐generation sequence (NGS) in our case showed TET2 and SRSF2 mutations. Aims & Objectives: A 75-year male was evaluated for monocytosis and thrombocytopenia. CBC showed Hb-11.8g/dl, TLC-12,060/cmm, Monocytes-35%, Platelets-39,000/cmm. Materials & Methods: Bone marrow examination showed a hypercellular marrow with myeloid series showing sequential maturation up to neutrophils with 30% monocytes. Immunophenotyping by flow cytometry from bone marrow had 3% blasts. Making chronic myelomonocytic leukemia as the likely diagnosis. NGS for myeloid mutation panel had TET2 (48.9%) and SRSF2 (32.5%) mutations. This report further supported the diagnosis of CMML. To fulfil the WHO diagnostic criteria for CMML, a BCR ABL1 by RQ-PCR was sent. The report came positive for p210 (B3A2, B2A2) Major Transcript (M-BCR) % IS of 38.418. Result: The patient was counselled regarding the unique presentation of the presence of 2 clones- P210 CML and CMML. After discussion with an international faculty with vast experience in CMML. It was decided to start this elderly gentleman on Imatinib 200mg and not on azacytidine, as ASXL1 was not present; hence, his chances of progressing to AML would be less and on the other end, if CML is left untreated then chances of progression to blast phase would always be a possibility. After 3 months on Imatinib his platelet count improved to 80,000 to 90,000/cmm, but his monocytosis persists. His 3rd month BCR-ABL1 IS% is 0.004%. Conclusion: After searching the literature, there were no case reports of a coexisting CML p210 with CMML. This case might be the first case report. p190 BCR ABL1 is often associated with monocytosis. There are few case reports of p210 BCR ABL1 positivity in patients with monocytosis but none with coexisting CMML. This case highlights the need for extensively evaluating patients with monocytosis with next-generation sequencing for myeloid mutation panel and BCR-ABL1 by RT-PCR to correctly diagnose and treat them.

Keywords: CMML, NGS, p190 CML, Imatinib

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Authors: Maad Kamal Al-Anni

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This study is about an algorithmic dependence of Artificial Neural Network on Multilayer Perceptron (MPL) pertaining to the classification and clustering presentations for Mobile Adhoc Network vulnerabilities. Moreover, mobile ad hoc network (MANET) is ubiquitous intelligent internetworking devices in which it has the ability to detect their environment using an autonomous system of mobile nodes that are connected via wireless links. Security affairs are the most important subject in MANET due to the easy penetrative scenarios occurred in such an auto configuration network. One of the powerful techniques used for inspecting the network packets is Intrusion Detection System (IDS); in this article, we are going to show the effectiveness of artificial neural networks used as a machine learning along with stochastic approach (information gain) to classify the malicious behaviors in simulated network with respect to different IDS techniques. The monitoring agent is responsible for detection inference engine, the audit data is collected from collecting agent by simulating the node attack and contrasted outputs with normal behaviors of the framework, whenever. In the event that there is any deviation from the ordinary behaviors then the monitoring agent is considered this event as an attack , in this article we are going to demonstrate the  signature-based IDS approach in a MANET by implementing the back propagation algorithm over ensemble-based Traffic Table (TT), thus the signature of malicious behaviors or undesirable activities are often significantly prognosticated and efficiently figured out, by increasing the parametric set-up of Back propagation algorithm during the experimental results which empirically shown its effectiveness  for the ratio of detection index up to 98.6 percentage. Consequently it is proved in empirical results in this article, the performance matrices are also being included in this article with Xgraph screen show by different through puts like Packet Delivery Ratio (PDR), Through Put(TP), and Average Delay(AD).

Keywords: Intrusion Detection System (IDS), Mobile Adhoc Networks (MANET), Back Propagation Algorithm (BPA), Neural Networks (NN)

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Authors: Sherry Junette Tagle

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Extensive research continues to prove the positive effects of home and school collaborations in education. Although parent involvement programs in Benguet, Philippines are in place, the impact has yet to affect the current aggregate performance of elementary pupils. This study describes the involvement of public elementary teachers and parents along Epstein’s types of involvement using the sequential explanatory design. Survey and interview results show that teachers place greater value on activities that cater to communicating, volunteering, learning at home and decision making. On the other hand, parents are actively involved in all six types and value the importance of their involvement in school to their child’s schooling. Parents of grades 1-4 pupils significantly give importance to communicating activities to offset difficulties encountered by young pupils while parents of grades 5-6 pupils, have declining interest in volunteering and learning at home activities citing older children as being more independent to do teacher-assigned tasks. Teachers, compared to the other respondent groups, significantly place higher value on the importance of parent leaders as their partners in implementing school activities. In general, involvement of parents and teachers in home-school activities is intensive in the lower grade levels and decreases as their child progresses through school. A recommended program for future collaborations of the Philippine’s Department of Education has been formulated to diversify existing activities and elicit greater participation among the school’s stakeholders to achieve holistic development of the pupils and ultimately improve pupils’ school aggregate performance.

Keywords: Epstein's types of involvement, community collaborations, home and school partnerships, parent involvement

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Authors: Ifeoluwa Omotehinse Oloruntoba

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Through comparative and causal models of translation, this paper examined the translation of ‘bread’ into the Yoruba language in three Yoruba versions of the Bible: Bibeli Yoruba Atoka (YBA), Bibeli Mimo ni Ede Yoruba Oni (BMY) and Bibeli Mimo (BM). In biblical times, bread was a very important delicacy that it was synonymous with food in general and in the Bible, bread sometimes refers to a type of food (a mixture of flour, water, and yeast that is baked) or food in general. However, this is not the case in the Yoruba culture. In fact, some decades ago, bread was not known in Nigeria and had no name in the Yoruba language until the 1900s when it was codified as burẹdi in Yoruba, a term borrowed from English and transliterated. Nevertheless, in Nigeria presently, bread is not a special food and it is not appreciated or consumed like in the West. This makes it difficult to translate bread in the Bible into Yoruba. From an investigation on the translation of this term, it was discovered that bread which has 330 occurrences in the English Bible translation (King James) has few occurrences in the three Yoruba Bible versions. In the first version (YBA) published in the 1880s, where bread is synonymous with food in general, it is mostly translated as oúnjẹ (food) or the verb jẹ (to eat), revealing that something is eaten but not indicating what it is. However, when the bread is a type of food, it is rendered as akara, a special delicacy of the Yoruba people made from beans flour. In the later version (BMY) published in the 1990s, bread as food, in general, is also mainly translated as oúnjẹ or the verb jẹ, but when it is a type of food, it is translated as akara with few occurrences of burẹdi. In the latest edition (BM), bread as food is either rendered as ounje or literally translated as burẹdi. Where it is a type of food in this version, it is mainly rendered as burẹdi with few occurrences of akara, indicating the assimilation of bread into the Yoruba culture. This result, although limited, shows that the Bible was translated into Yoruba to make it accessible to Yoruba speakers in their everyday language, hence the application of both domesticating and foreignising strategies. This research also emphasizes the role of the translator as an intermediary between two cultures.

Keywords: translation, Bible, Yoruba, cultural problems

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Authors: Vahid Ebrahimipour

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Word representation and context meaning of text-based documents play an essential role in knowledge modeling. Business procedures written in natural language are meant to store technical and engineering information, management decision and operation experience during the production system life cycle. Context meaning representation is highly dependent upon word sense, lexical relativity, and sematic features of the argument. This paper proposes a method for lexical semantic analysis and context meaning representation of maintenance activity in a mass production system. Our approach constructs a straightforward lexical semantic approach to analyze facilitates semantic and syntactic features of context structure of maintenance report to facilitate translation, interpretation, and conversion of human-readable interpretation into computer-readable representation and understandable with less heterogeneity and ambiguity. The methodology will enable users to obtain a representation format that maximizes shareability and accessibility for multi-purpose usage. It provides a contextualized structure to obtain a generic context model that can be utilized during the system life cycle. At first, it employs a co-occurrence-based clustering framework to recognize a group of highly frequent contextual features that correspond to a maintenance report text. Then the keywords are identified for syntactic and semantic extraction analysis. The analysis exercises causality-driven logic of keywords’ senses to divulge the structural and meaning dependency relationships between the words in a context. The output is a word contextualized representation of maintenance activity accommodating computer-based representation and inference using OWL/RDF.

Keywords: lexical semantic analysis, metadata modeling, contextual meaning extraction, ontology modeling, knowledge representation

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Authors: Hannah K. M. Tang, Muhammad Ateeq, Mark J. Lake, Badr Abdullah, Frederic A. Bezombes

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There is little research applying virtual reality (VR) to the treatment of musculoskeletal injury in athletes. This is despite their prevalence, and the implications for physical and psychological health. Nevertheless, developments of wireless VR headsets better facilitate dynamic movement in VR environments (VREs), and more research is expected in this emerging field. This systematic review identified publications that used VR interventions for the analysis or treatment of lower-limb musculoskeletal injury of athletes. It established a search protocol, and through narrative discussion, identified existing trends. Database searches encompassed four term sets: 1) VR systems; 2) musculoskeletal injuries; 3) sporting population; 4) movement outcome analysis. Overall, a total of 126 publications were identified through database searching, and twelve were included in the final analysis and discussion. Many of the studies were pilot and proof of concept work. Seven of the twelve publications were observational studies. However, this may provide preliminary data from which clinical trials will branch. If specified, the focus of the literature was very narrow, with very similar population demographics and injuries. The trends in the literature findings emphasised the role of VR and attentional focus, the strategic manipulation of movement outcomes, and the transfer of skill to the real-world. Causal inferences may have been undermined by flaws, as most studies were limited by the practicality of conducting a two-factor clinical-VR-based study. In conclusion, by assessing the exploratory studies, and combining this with the use of numerous developments, techniques, and tools, a novel application could be established to utilise VR with dynamic movement, for the effective treatment of specific musculoskeletal injuries of athletes.

Keywords: athletes, lower-limb musculoskeletal injury, rehabilitation, return-to-sport, virtual reality

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Authors: Velly Anatasia

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In the last few decades extensive research has been conducted into information technology (IT) adoption, testing a series of factors considered to be essential for improved diffusion. Some studies analyze IT characteristics such as usefulness, ease of use and/or security, others focus on the emotions and experiences of users and a third group attempts to determine the importance of socioeconomic user characteristics such as gender, educational level and income. The situation is similar regarding e-commerce, where the majority of studies have taken for granted the importance of including these variables when studying e-commerce adoption, as these were believed to explain or forecast who buys or who will buy on the internet. Nowadays, the internet has become a marketplace suitable for all ages and incomes and both genders and thus the prejudices linked to the advisability of selling certain products should be revised. The objective of this study is to test whether the socioeconomic characteristics of experienced e-shoppers such as gender rally moderate the effect of their perceptions of online shopping behavior. Current development of the online environment and the experience acquired by individuals from previous e-purchases can attenuate or even nullify the effect of these characteristics. The individuals analyzed are experienced e-shoppers i.e. individuals who often make purchases on the internet. The Technology Acceptance Model (TAM) was broadened to include previous use of the internet and perceived self-efficacy. The perceptions and behavior of e-shoppers are based on their own experiences. The information obtained will be tested using questionnaires which were distributed and self-administered to respondent accustomed using internet. The causal model is estimated using structural equation modeling techniques (SEM), followed by tests of the moderating effect of socioeconomic variables on perceptions and online shopping behavior. The expected findings of this study indicated that gender moderate neither the influence of previous use of the internet nor the perceptions of e-commerce. In short, they do not condition the behavior of the experienced e-shopper.

Keywords: Internet shopping, age groups, gender, income, electronic commerce

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Authors: S. I. Enem, S. I. Oboegbulem

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Objective: The most frequently implicated E. coli serotype causing haemorrhagic colitis and haemorrhagic uraemic syndrome (HUS) is VTEC 0157. However, non-O157 VTEC is now known to be as prevalent as VETC O157 infection (or even more) in most parts of the world. The objective of the study was to establish the occurrence of non-O157 VTEC serotypes in cattle in the Federal Capital Territory (FCT) Abuja, Nigeria. The level of significance of the infection with sex, age and season were also tested. Methods: The study was carried out in the FCT, Abuja, Nigeria which is located between latitude 8o and 90 25` North of the equator and longitude 60 45` and 7045` East of the Greenwich meridian. The cross sectional epidemiological method and multi-staged sampling technique were used in this study. Samples were collected from the freshly voided faeces of both apparently healthy and diarrhoeic cattle in selected abattoirs and cattle herds. Enriched samples were analyzed bacteriologically and biochemically after which they were characterised using commercially prepared latex agglutination test kits. Results: A total of 718 faecal samples from cattle were analyzed for the presence of VTEC non-O157. Thirty eight (5.23%) were positive for non-O157. There was no significant association (p > 0.05) between sex and infection with non-O157 VTEC in cattle. There was a significant association (P < 0.05) between age and infection with non-O157 VTEC in cattle. Calves were more associated than the adults. There was also a significant association (P < 0.05) between season and infection with non-O157 VTEC in cattle. The dry season was more associated than the wet season. Conclusion: The study established the occurrence and prevalence of non-O157 VTEC in cattle in FCT, Abuja, Nigeria. As a major food animal in Nigeria, infection in cattle provides an epidemiological causal association to the infection in humans. The result showed that warmer seasons (dry season) stimulate the presence of VTEC infection in animals and thus, as a consequence, increases the number of human cases. The prevalence was also higher in younger calves (< 6 months) probably as a result of undeveloped immune system.

Keywords: prevalence, distribution, Verocytotoxigenic escherichia coli (VTEC), non-O157 serotypes, cattle

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Authors: Ambrish Tiwari, Sudhasini Panda, Archana Singh, Kalpana Luthra, S. K. Sharma

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Introduction: On the basis of available literature we know that various host factors play a role in outcome of Tuberculosis (TB) infection by modulating innate immunity. One such factor is Inducible Nitric Oxide Synthase enzyme (iNOS) which help in the production of Nitric Oxide (NO), an antimicrobial agent. Expression of iNOS is in control of various host factors in which Vitamin D along with its nuclear receptor Vitamin D receptor (VDR) is one of them. Vitamin D along with its receptor also produces cathelicidin (antimicrobicidal agent). With this background, we attempted to investigate the levels of Vitamin D and NO along with their associated molecules in tuberculosis patients and household contacts as compared to healthy controls and assess the implication of these findings in susceptibility to tuberculosis (TB). Study subjects and methods: 100 active TB patients, 75 household contacts, and 70 healthy controls were taken. VDR and iNOS mRNA levels were studied using real-time PCR. Serum VDR, cathelicidin, iNOS levels were measured using ELISA. Serum Vitamin D levels were measured in serum samples using chemiluminescence based immunoassay. NO was measured using colorimetry based kit. Results: VDR and iNOS mRNA levels were found to be lower in active TB group compared to household contacts and healthy controls (P=0.0001 and 0.005 respectively). The serum levels of Vitamin D were also found to be lower in active TB group as compared to healthy controls (P =0.001). Levels of cathelicidin and NO was higher in patient group as compared to other groups (p=0.01 and 0.5 respectively). However, the expression of VDR and iNOS and levels of vitamin D was significantly (P < 0.05) higher in household contacts compared to both active TB and healthy control groups. Inference: Higher levels of Vitamin D along with VDR and iNOS expression in household contacts as compared to patients suggest that vitamin D might have a protective role against TB which prevents activation of the disease. From our data, we can conclude that decreased vitamin D levels could be implicated in disease progression and we can use cathelicidin and NO as a biomarker for early diagnosis of pulmonary tuberculosis.

Keywords: vitamin D, VDR, iNOS, tuberculosis

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Authors: Lulu Liao, Huijing Chen, Yinan Zhao, Hongting Ning, Hui Feng

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Urinary tract infection rate is an important index of care quality in nursing homes. The aim of the study is to understand the nursing assistant's current knowledge and attitudes of urinary incontinence and to explore related stakeholders' viewpoint about urinary incontinence training. This explanatory sequential study used Knowledge, Practice, and Attitude Model (KAP) and Adult Learning Theories, as the conceptual framework. The researchers collected data from 509 nursing assistants in sixteen nursing homes in Hunan province in China. The questionnaire survey was to assess the knowledge and attitude of urinary incontinence of nursing assistants. On the basis of quantitative research and combined with focus group, training demands were identified, which nurse managers should adopt to improve nursing assistants’ professional practice ability in urinary incontinence. Most nursing assistants held the poor knowledge (14.0 ± 4.18) but had positive attitudes (35.5 ± 3.19) toward urinary incontinence. There was a significant positive correlation between urinary incontinence knowledge and nursing assistants' year of work and educational level, urinary incontinence attitude, and education level (p < 0.001). Despite a general awareness of the importance of prevention of urinary tract infections, not all nurse managers fully valued the training in urinary incontinence compared with daily care training. And the nursing assistants required simple education resources to equip them with skills to address problem about urinary incontinence. The variety of learning methods also highlighted the need for educational materials, and nursing assistants had shown a strong interest in online learning. Related education material should be developed to meet the learning need of nurse assistants and provide suitable training method for planned quality improvement in urinary incontinence.

Keywords: mixed methods, nursing assistants, nursing homes, urinary incontinence

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Authors: Erika Takidah, Salina Kassim

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Digital transformation has accelerated in the new millennium. It is reshaping the financial services industry from a traditional system to financial technology. Moreover, the number of financial inclusion rates in Indonesia is less than 60%. An innovative model needed to elucidate this national problem. On the other hand, the Islamic financial service industry and financial technology grow fast as a new aspire in economic development. An Islamic bank, takaful, Islamic microfinance, Islamic financial technology and Islamic social finance institution could collaborate to intensify the financial inclusion number in Indonesia. The primary motive of this paper is to examine the strategy of collaboration-based Islamic financial services to enhance financial inclusion in Indonesia, particularly facing the digital era. The fundamental findings for the main problems are the foundations and key ecosystems aspect involved in the development of collaboration-based Islamic financial services. By using the Interpretive Structural Model (ISM) approach, the core problems faced in the development of the models have lacked policy instruments guarding the collaboration-based Islamic financial services with fintech work process and availability of human resources for fintech. The core strategies or foundations that are needed in the framework of collaboration-based Islamic financial services are the ability to manage and analyze data in the big data era. For the aspects of the Ecosystem or actors involved in the development of this model, the important actor is government or regulator, educational institutions, and also existing industries (Islamic financial services). The outcome of the study designates that strategy collaboration of Islamic financial services institution supported by robust technology, a legal and regulatory commitment of the regulators and policymakers of the Islamic financial institutions, extensive public awareness of financial inclusion in Indonesia. The study limited itself to realize financial inclusion, particularly in Islamic finance development in Indonesia. The study will have an inference for the concerned professional bodies, regulators, policymakers, stakeholders, and practitioners of Islamic financial service institutions.

Keywords: collaboration, financial inclusion, Islamic financial services, Islamic fintech

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Authors: Hung-Sheng Lin, Cheng-Hsuan Li

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Over the past few years, kernel-based algorithms have been widely used to extend some linear feature extraction methods such as principal component analysis (PCA), linear discriminate analysis (LDA), and nonparametric weighted feature extraction (NWFE) to their nonlinear versions, kernel principal component analysis (KPCA), generalized discriminate analysis (GDA), and kernel nonparametric weighted feature extraction (KNWFE), respectively. These nonlinear feature extraction methods can detect nonlinear directions with the largest nonlinear variance or the largest class separability based on the given kernel function. Moreover, they have been applied to improve the target detection or the image classification of hyperspectral images. The double nearest proportion feature extraction (DNP) can effectively reduce the overlap effect and have good performance in hyperspectral image classification. The DNP structure is an extension of the k-nearest neighbor technique. For each sample, there are two corresponding nearest proportions of samples, the self-class nearest proportion and the other-class nearest proportion. The term “nearest proportion” used here consider both the local information and other more global information. With these settings, the effect of the overlap between the sample distributions can be reduced. Usually, the maximum likelihood estimator and the related unbiased estimator are not ideal estimators in high dimensional inference problems, particularly in small data-size situation. Hence, an improved estimator by shrinkage estimation (regularization) is proposed. Based on the DNP structure, LDA is included as a special case. In this paper, the kernel method is applied to extend DNP to kernel-based DNP (KDNP). In addition to the advantages of DNP, KDNP surpasses DNP in the experimental results. According to the experiments on the real hyperspectral image data sets, the classification performance of KDNP is better than that of PCA, LDA, NWFE, and their kernel versions, KPCA, GDA, and KNWFE.

Keywords: feature extraction, kernel method, double nearest proportion feature extraction, kernel double nearest feature extraction

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Authors: S. Fahiminiya, J. Nadaf, F. Rauch, L. Jerome-Majewska, J. Majewski

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Background: Sequencing of protein coding regions of human genome (Whole Exome Sequencing; WES), has demonstrated a great success in the identification of causal mutations for several rare genetic disorders in human. Generally, most of WES studies have focused on rare variants in coding exons and splicing-sites where missense substitutions lead to the alternation of protein product. Although focusing on this category of variants has revealed the mystery behind many inherited genetic diseases in recent years, a subset of them remained still inconclusive. Here, we present the result of our WES studies where analyzing only rare variants in coding regions was not conclusive but further investigation revealed the involvement of non-coding variants and copy number variations (CNV) in etiology of the diseases. Methods: Whole exome sequencing was performed using our standard protocols at Genome Quebec Innovation Center, Montreal, Canada. All bioinformatics analyses were done using in-house WES pipeline. Results: To date, we successfully identified several disease causing mutations within gene coding regions (e.g. SCARF2: Van den Ende-Gupta syndrome and SNAP29: 22q11.2 deletion syndrome) by using WES. In addition, we showed that variants in non-coding regions and CNV have also important value and should not be ignored and/or filtered out along the way of bioinformatics analysis on WES data. For instance, in patients with osteogenesis imperfecta type V and in patients with glucocorticoid deficiency, we identified variants in 5'UTR, resulting in the production of longer or truncating non-functional proteins. Furthermore, CNVs were identified as the main cause of the diseases in patients with metaphyseal dysplasia with maxillary hypoplasia and brachydactyly and in patients with osteogenesis imperfecta type VII. Conclusions: Our study highlights the importance of considering non-coding variants and CNVs during interpretation of WES data, as they can be the only cause of disease under investigation.

Keywords: whole exome sequencing data, non-coding variants, copy number variations, rare diseases

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Authors: Robyn White, Juan Bornman, Ensa Johnson

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People with disabilities are at a high risk of becoming victims of crime. Individuals with little or no functional speech (LNFS) face an even higher risk. One way of reducing the risk of remaining a victim of crime is to face the alleged perpetrator in court as a witness – therefore it is important for a person with LNFS who has been a victim of crime to have the required vocabulary to testify in court. The aim of this study was to identify and describe the core and fringe legal vocabulary required by illiterate victims of crime, who have little or no functional speech, to testify in court as witnesses. A mixed-method, the exploratory sequential design consisting of two distinct phases was used to address the aim of the research. The first phase was of a qualitative nature and included two different data sources, namely in-depth semi-structured interviews and focus group discussions. The overall aim of this phase was to identify and describe core and fringe legal vocabulary and to develop a measurement instrument based on these results. Results from Phase 1 were used in Phase 2, the quantitative phase, during which the measurement instrument (a custom-designed questionnaire) was socially validated. The results produced six distinct vocabulary categories that represent the legal core vocabulary and 99 words that represent the legal fringe vocabulary. The findings suggested that communication boards should be individualised to the individual and the specific crime. It is believed that the vocabulary lists developed in this study act as a valid and reliable springboard from which communication boards can be developed. Recommendations were therefore made to develop an Alternative and Augmentative Communication Resource Tool Kit to assist the legal justice system.

Keywords: augmentative and alternative communication, person with little or no functional speech, sexual crimes, testifying in court, victim of crime, witness competency

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Authors: Yu-Che Cheng, Min-Lih Chang, Ke-Hao Cheng, Chuan-Cheng Wang

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Taiwan is an island located along the southeastern coast of the Asian continent, located between Japan and the Philippines. It is surrounded by the sea on all sides. However, due to the presence of the Central Mountain Range, the rivers on the east and west coasts of Taiwan are relatively short. This geographical feature results in a phenomenon where, despite having rainfall that is 2.6 times the world average, 58.5% of the rainwater flows into the ocean. Moreover, approximately 80% of the annual rainfall occurs between May and October, leading to distinct wet and dry periods. To address these challenges, Taiwan relies on large reservoirs, storage ponds, and groundwater extraction for water resource allocation. It is necessary to construct water treatment facilities at suitable locations to provide the population with a stable and reliable water supply. In general, the construction of a new water treatment plant requires careful planning and evaluation. The process involves acquiring land and issuing contracts for construction in a sequential manner. With the increasing severity of global warming and climate change, there is a heightened risk of extreme hydrological events and severe water situations in the future. In cases of urgent water supply needs in a region, relying on traditional lengthy processes for constructing water treatment plants might not be sufficient to meet the urgent demand. Therefore, this study aims to explore the use of simplified water treatment procedures and the construction of rapid "temporary water treatment plants" to tackle the challenges posed by extreme climate conditions (such as a century-long drought) and situations where water treatment plant construction cannot keep up with the pace of water source development.

Keywords: temporary water treatment plant, emergency water supply, construction site groundwater, drought

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Authors: Houda Oueriemmi, Petra Susan Kidd, Carmen Trasar-Cepeda, Beatriz Rodríguez-Garrido, Mohamed Moussa, Ángeles Prieto-Fernández, Mohamed Ouessar

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Organic amendments are generally used for improving the fertility of arid and semi-arid soils. However, the price of farmyard manure, the organic amendment typically applied to many arid and semi-arid soils has highly increased in the last years. To investigate at field scale whether cheap, highly available organic amendments, such as sewage sludge compost and municipal solid waste compost, may be acceptable as substitutes for farmyard manure is therefore of great interest. A field plots experiment was carried out to assess the effects of a single application of three organic amendments on soil fertility, distribution of trace elements and on barley yield. Municipal solid waste compost (MSWC), farmyard manure (FYM) and sewage sludge compost (SSC) were applied at rates of 0, 20, 40 and 60 t ha⁻¹, and barley was cultivated in two consecutive years. Plant samples and soils were collected for laboratory analyses after two consecutive harvests. Compared with unamended soil, the application of the three organic residues improved the fertility of the topsoil, showing a significant dose-dependent increase of TOC, N, P contents up to the highest dose of 60 t ha⁻¹ (0.74%, 0.06% and 40 mg kg⁻¹, respectively). The enhancement of soil nutrient status impacted positively on grain yield (up to 51%). The distribution of trace elements in the soil, analysed by a sequential extraction procedure, revealed that the MSWC increased the acid-extractable Co and Cu and reducible Ni, while SSC increased reducible Co and Ni and oxidisable Cu, relative to the control soil.

Keywords: municipal solid waste compost, sewage sludge compost, fertility, trace metals

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Authors: Ella Sèdé Maforikan

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Sustained water management requires quantitative information and the knowledge of spatiotemporal dynamics of hydrological system within the basin. This can be achieved through the research. Several studies have investigated both surface water and groundwater in Beterou catchment. However, there are few published papers on the application of the SWAT modeling in Beterou catchment. The objective of this study was to evaluate the performance of SWAT to simulate the water balance within the watershed. The inputs data consist of digital elevation model, land use maps, soil map, climatic data and discharge records. The model was calibrated and validated using the Sequential Uncertainty Fitting (SUFI2) approach. The calibrated started from 1989 to 2006 with four years warming up period (1985-1988); and validation was from 2007 to 2020. The goodness of the model was assessed using five indices, i.e., Nash–Sutcliffe efficiency (NSE), the ratio of the root means square error to the standard deviation of measured data (RSR), percent bias (PBIAS), the coefficient of determination (R²), and Kling Gupta efficiency (KGE). Results showed that SWAT model successfully simulated river flow in Beterou catchment with NSE = 0.79, R2 = 0.80 and KGE= 0.83 for the calibration process against validation process that provides NSE = 0.78, R2 = 0.78 and KGE= 0.85 using site-based streamflow data. The relative error (PBIAS) ranges from -12.2% to 3.1%. The parameters runoff curve number (CN2), Moist Bulk Density (SOL_BD), Base Flow Alpha Factor (ALPHA_BF), and the available water capacity of the soil layer (SOL_AWC) were the most sensitive parameter. The study provides further research with uncertainty analysis and recommendations for model improvement and provision of an efficient means to improve rainfall and discharges measurement data.

Keywords: watershed, water balance, SWAT modeling, Beterou

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Authors: Debit Datta, Jeffrey J. Coleman, Scott A. Enebak, Lori G. Eckhardt

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Loblolly pine (Pinus taeda) is a leading productive timber species in the southeastern USA. Over the past three years, an emerging threat is expressed by successive needle defoliation followed by stunted growth and tree mortality in loblolly pine plantations. Considering economic significance, it has now become a rising concern among landowners, forest managers, and forest health state cooperators. However, the symptoms of the disease were perplexed somewhat with root disease(s) and recurrently attributed to invasive Phytophthora species due to the similarity of disease nature and devastation. Therefore, the study investigated the potential causal agent of this disease and characterized the fungi associated with loblolly pine needle defoliation in the southeastern USA. Besides, 70 trees were selected at seven long-term monitoring plots at Chatom, Alabama, to monitor and record the annual disease incidence and severity. Based on colony morphology and ITS-rDNA sequence data, a total of 28 species of fungi representing 17 families have been recovered from diseased loblolly pine needles. The native brown-spot pathogen, Lecanosticta acicola, was the species most frequently recovered from unhealthy loblolly pine needles in combination with some other common needle cast and rust pathogen(s). Identification was confirmed using morphological similarity and amplification of translation elongation factor 1-alpha gene region of interest. Tagged trees were consistently found chlorotic and defoliated from 2019 to 2020. The current emergence of the brown-spot pathogen causing loblolly pine mortality necessitates the investigation of the role of changing climatic conditions, which might be associated with increased pathogen pressure to loblolly pines in the southeastern USA.

Keywords: brown-spot needle blight, loblolly pine, needle defoliation, plantation forestry

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Authors: Gayathri Nagarajan, L. D. Dhinesh Babu

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Health care is one of the prominent industries that generate voluminous data thereby finding the need of machine learning techniques with big data solutions for efficient processing and prediction. Missing data, incomplete data, real time streaming data, sensitive data, privacy, heterogeneity are few of the common challenges to be addressed for efficient processing and mining of health care data. In comparison with other applications, accuracy and fast processing are of higher importance for health care applications as they are related to the human life directly. Though there are many machine learning techniques and big data solutions used for efficient processing and prediction in health care data, different techniques and different frameworks are proved to be effective for different applications largely depending on the characteristics of the datasets. In this paper, we present a framework that uses ensemble machine learning technique gradient boosted trees for data classification in health care big data. The framework is built on Spark platform which is fast in comparison with other traditional frameworks. Unlike other works that focus on a single technique, our work presents a comparison of six different machine learning techniques along with gradient boosted trees on datasets of different characteristics. Five benchmark health care datasets are considered for experimentation, and the results of different machine learning techniques are discussed in comparison with gradient boosted trees. The metric chosen for comparison is misclassification error rate and the run time of the algorithms. The goal of this paper is to i) Compare the performance of gradient boosted trees with other machine learning techniques in Spark platform specifically for health care big data and ii) Discuss the results from the experiments conducted on datasets of different characteristics thereby drawing inference and conclusion. The experimental results show that the accuracy is largely dependent on the characteristics of the datasets for other machine learning techniques whereas gradient boosting trees yields reasonably stable results in terms of accuracy without largely depending on the dataset characteristics.

Keywords: big data analytics, ensemble machine learning, gradient boosted trees, Spark platform

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Authors: Iva Trako, Maris Micaela Sviatschi, Guadalupe Kavanaugh

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Domestic violence is a major concern in developing countries, with important social, economic and health consequences. However, institutions do not usually address the problems facing women or ethnic and religious minorities. For example, the police do very little to stop domestic violence in rural areas of developing countries. This paper exploits the introduction of women’s justice centers (WJCs) in Peru to provide causal estimates on the effects of improving access to justice for women and children. These centers offer a new integrated public service model for women by including medical, psychological and legal support in cases of violence against women. Our empirical approach uses a difference in difference estimation exploiting variation over time and space in the opening of WJC together with province-by-year fixed effects. Exploiting administrative data from health providers and district attorney offices, we find that after the opening of these centers, there are important improvements on women's welfare: a large reduction in femicides and female hospitalizations for assault. Moreover, using geo-coded household surveys we find evidence that the existence of these services reduces domestic violence, improves women's health, increases women's threat points and, therefore, lead to household decisions that are more aligned with their interests. Using administrative data on the universe of schools, we find large gains on human capital for their children: affected children are more likely to enroll, attend school and have better grades in national exams, instead of working for the family. In sum, the evidence in this paper shows that providing access to justice for women can be a powerful tool to reduce domestic violence and increase education of children, suggesting a positive inter-generational benefit.

Keywords: access to justice, domestic violence, education, household bargaining

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Authors: Mohammadreza Hajialigol, Nargues Falahi Charkhabi, Fatemeh Shahryari, Saadat Sarikhani

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BACKGROUND AND OBJECTIVES Iran is the third producer of Persian walnut worldwide. However, its walnut trees have been under threat from decline during last decade. Walnut canker caused by B. nigrifluens and B. rubrifaciens was recorded in multiple regions of Iran. Furthermore, Brenneria rosae subsp. rosae and Gibbsiella quercinecans were recently recognized as responsible for walnut decline in northwestern Iran. This study aimed to identify the causal agent of walnut decline in Kermanshah and Isfahan. MATERIAL AND METHODS Symptomatic samples were collected from affected walnut trees of Kermanshah and Isfahan provinces. The pathogenicity of strains was proved on immature walnut fruits cv. ‘Hartley’ and young green twigs of two-year-old walnut seedling cv. ‘Chandler’. Pathogenic strains were subjected to conventional phenotypic tests. 16S rRNA, gyrB, and infB genes were partially amplified and sequenced. RESULTS Irregular longitudinal cankers and dark lesions were observed in the outer and inner bark, respectively. Twenty-four strains were isolated on EMB-agar media. Fourteen strains were able to cause necrosis and a dark-colored region in the mesocarp and on young green twigs around the inoculation site 14 and 30 days post-inoculation, respectively. Strains were able to hydrolyze Tween 20, Tween 80, gelatin and esculin, however, did not produce indole or urease. Pairwise comparison, the 16S rRNA gene nucleotide sequences of strain I2 were 100% identical with those of Rahnella victoriana FRB 225T. Moreover, a phylogenetic tree reconstructed based on the concatenated sequences of two housekeeping gene fragments, gyrB (601 bp) and infB (615 bp), revealed that the strains I2, I5, and KE6 were clustered with R. victoriana FRB 225T. CONCLUSION To the best of our knowledge, this is the first report of R. victoriana in association with walnut decline. This result is necessary to find resistant genotypes.

Keywords: emerging pathogens, Iran, juglans regia, MLSA

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Authors: Milagros S. Salibad, Levita B. Grana

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The presence and role of Indigenous Peoples (IPs) residing in key biodiversity, protected, and watershed areas within the ancestral domain in the Caraga region, Mindanao, Philippines, hold immense significance. Recognizing their importance and rights, this study aimed to determine the level of biodiversity conservation practices and extent of environmental stewardship among the Mamanwas, Manobos, and Higaonons, assess potential differences in these practices, and identify factors that facilitate or hinder them. Employing an explanatory sequential mixed-method research design, 421 respondents participated through a researcher-made questionnaire. Additional data were collected through focus group discussions, key informant interviews, researcher field notes, community immersions, and secondary sources. The results revealed a high level of biodiversity conservation practices across the three IP groups, with variations influenced by their cultural and traditional practices, awareness, and access to resources and information. Each group exhibited unique environmental practices shaped by their distinct cultures, traditions, and customary knowledge. They have a strong sense of ownership and responsibility towards their ancestral lands and territories and adopt traditional knowledge and practices that promote sustainable resource management and biodiversity conservation. These practices align with the Indigenous Peoples Rights Act (IPRA), also known as Republic Act No. 8371. Various facilitating and hindering factors influenced their conservation efforts. To uphold the region's biodiversity resources, it is recommended that government agencies continue to evaluate and monitor the sustainability of IPs' local biodiversity conservation practices. Additionally, efforts should be made to involve IP communities as essential contributors and stakeholders in these conservation endeavors.

Keywords: biodiversity, conservation, indigenous peoples, traditional knowledge, environmental stewardship

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Authors: Ayushi Modi, Eliot Bochet-Merand

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This study investigates the structural determinants of green strategies among Small and Medium Enterprises (SMEs) in the European Union and select countries, utilizing data from the Flash Eurobarometer 498 - SMEs, Resource Efficiency, and Green Markets. By applying sequential logit analysis, we explore the drivers behind the adoption and scaling of green actions, such as resource efficiency, waste management, and product innovation, while also examining the provision of green products and services. A key contribution of this research is the novel distinction between the process stage (green actions) and the product stage (green outputs), allowing for a deeper analysis of how green initiatives translate into sustainable business outcomes. Our findings reveal that structural characteristics, such as firm size, sector, and turnover growth, significantly influence the likelihood of both providing green products and implementing comprehensive green actions. Smaller, younger firms in high-impact sectors like construction and industry are more likely to engage in sustainability efforts, particularly when they have a green strategy and a dedicated green workforce. Furthermore, companies serving B2B and B2C clients and experiencing turnover growth are more inclined to offer green products. The study underscores the economic implications of these insights, suggesting that financial flexibility, strategic commitment, and human capital investments are critical for scaling green initiatives. By refining variables and excluding heterogeneous countries, our data management ensures robust results. This research provides novel insights into the distinct roles of process and product stages in sustainability, offering valuable policy recommendations for promoting environmental performance in SMEs.

Keywords: green strategy, resource efficiency, SMES, sustainability, product innovation, environmental performance

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Authors: Oscar E. Cariceo, Claudia V. Casal

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Machine learning offers a set of techniques to promote social work interventions and can lead to support decisions of practitioners in order to predict new behaviors based on data produced by the organizations, services agencies, users, clients or individuals. Machine learning techniques include a set of generalizable algorithms that are data-driven, which means that rules and solutions are derived by examining data, based on the patterns that are present within any data set. In other words, the goal of machine learning is teaching computers through 'examples', by training data to test specifics hypothesis and predict what would be a certain outcome, based on a current scenario and improve that experience. Machine learning can be classified into two general categories depending on the nature of the problem that this technique needs to tackle. First, supervised learning involves a dataset that is already known in terms of their output. Supervising learning problems are categorized, into regression problems, which involve a prediction from quantitative variables, using a continuous function; and classification problems, which seek predict results from discrete qualitative variables. For social work research, machine learning generates predictions as a key element to improving social interventions on complex social issues by providing better inference from data and establishing more precise estimated effects, for example in services that seek to improve their outcomes. This paper exposes the results of a classification algorithm to predict cyberbullying among adolescents. Data were retrieved from the National Polyvictimization Survey conducted by the government of Chile in 2017. A logistic regression model was created to predict if an adolescent would experience cyberbullying based on the interaction and behavior of gender, age, grade, type of school, and self-esteem sentiments. The model can predict with an accuracy of 59.8% if an adolescent will suffer cyberbullying. These results can help to promote programs to avoid cyberbullying at schools and improve evidence based practice.

Keywords: cyberbullying, evidence based practice, machine learning, social work research

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Authors: Kiran Nawaz, Waheed Anwar, Sehrish Iftikhar, Muhammad Nasir Subhani, Ahmad Ali Shahid

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Plant growth promoting rhizobacteria (PGPR) have been extensively studied and applied for the biocontrol of many soilborne diseases. These rhizobacteria are very efficient against root rot and many other foliar diseases associated with solanaceous plants. These bacteria may inhibit the growth of various pathogens through direct inhibition of target pathogens or indirectly by the initiation of systemic resistance (ISR) which is active all over the complete plant. In the present study, 20 different rhizobacterial isolates were recovered from the root zone of healthy chili plants. All soil samples were collected from various chili-growing areas in Punjab. All isolated rhizobacteria species were evaluated in vitro and in vivo against Phytophthora capsici. Different species of Bacillus and Pseudomonas were tested for the antifungal activity against P. capsici the causal organism of Root rot disease in different crops together with chili. Dual culture and distance culture bioassay were carried out to study the antifungal potential of volatile and diffusible metabolites secreted from rhizobacteria. After seven days of incubation at 22°C, growth inhibition rate was recorded. Growth inhibition rate depended greatly on the tested bacteria and screening methods used. For diffusible metabolites, inhibition rate was 35-62% and 20-45% for volatile metabolites. The screening assay for plant growth promoting and disease inhibition potential of chili associated PGPR indicated 42-100% reduction in disease severity and considerable enhancement in roots fresh weight by 55-87%, aerial parts fresh weight by 35-65% and plant height by 65-76% as compared to untreated control and pathogen-inoculated plants. Pseudomonas flourescene, B. thuringiensis, and B. subtilis were found to be the most efficient isolates in inhibiting P. capsici radial growth, increase plant growth and suppress disease severity.

Keywords: rhizobacteria, chili, phytophthora, root rot

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Authors: Mohammadreza Hajialigol, Nargues Falahi Charkhabi, Fatemeh Shahryari, Saadat Sarikhani

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BACKGROUND AND OBJECTIVES Walnut canker is characterized by brown to blackish roundish blotches on the trunks and main branches, necrosis of inner bark and bleeding with dark brown to black-colored exudates. The present study aimed to identify the causative agents of walnut decline by their phenotypic features, approval of pathogenicity, the partial sequencing of the housekeeping genes in Razavi Khorasan. MATERIAL AND METHODS Ten Symptomatic samples were collected from walnut orchards of Razavi Khorasan in 2019. Pathogenicity of all isolated strains was carried out on walnut immature fruits cv. ‘Hartley’ and young green twigs of cv. ‘Chandler’. All pathogenic strains were subjected to physiological, morphological and biochemical tests. 16S rRNA and housekeeping genes (fusA, leuS, and pyrG) were partially amplified and sequenced. RESULTS Eight strains were able to cause necrosis and a dark-colored region in the mesocarp of immature walnut fruits, and three representative strains caused necrosis on young inoculated twigs. Strains utilized starch, however, did not utilized esculin, Tween 20, Tween 80, and gelatin. The partial 16S rRNA gene sequence of strain KH7 indicated 99.63 % similarity to that of Citrobacter braakii ATCC5113T. The phylogenetic analyses based on the partial sequencing of three housekeeping genes, fusA (633 bp), pyrG (305), and leuS (640 bp), demonstrated that strains KH1, KH3, and KH7 belong to C. braakii species in a monophyletic clade with high bootstrap support. CONCLUSION To the best of our knowledge, this is the first report of C. braakii as a new plant pathogen which cause walnut decline. Identification of bacteria associated with walnut decline will eventually improve our understanding of the etiology of the disease and may result in improved management techniques for control.

Keywords: emerging pathogens, Iran, juglans regia, MLSA

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Authors: Bello, A., Muhammed Ibrahim Abba., Abdullahi, M., Dauda, Sabo, & Shittu, A. T.

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This study investigated the Predictors of Lecturers Knowledge Sharing Acceptance on Open Educational Resources (OER) in North-East Nigerian in Universities. The study population comprised of 632 lecturers of Federal Universities in North-east Nigeria. The study sample covered 338 lecturers who were selected purposively from Adamawa, Bauchi and Borno State Federal Universities in Nigeria. The study adopted a prediction correlational research design. The instruments used for data collection was the questionnaire. Experts in the field of educational technology validated the instrument and tested it for reliability checks using Cronbach’s alpha. The constructs on lecturers’ acceptance to share OER yielded a reliability coefficient of; α = .956 for Performance Expectancy, α = .925; for Effort Expectancy, α = .955; for Social Influence, α = .879; for Facilitating Conditions and α = .948 for acceptance to share OER. the researchers contacted the Deanery of faculties of education and enlisted local coordinators to facilitate the data collection process at each university. The data was analysed using multiple sequential regression statistic at a significance level of 0.05 using SPSS version 23.0. The findings of the study revealed that performance expectancy (β = 0.658; t = 16.001; p = 0.000), effort expectancy (β = 0.194; t = 3.802; p = 0.000), social influence (β = 0.306; t = 5.246; p = 0.000), collectively indicated that the variables have a predictive capacity to stimulate lecturer’s acceptance to share their resources on OER repository. However, the finding revealed that facilitating conditions (β = .053; t = .899; p = 0.369), does not have a predictive capacity to stimulate lecturer’s acceptance to share their resources on OER repository. Based on these findings, the study recommends among others that the university management should consider adjusting OER policy to be centered around actualizing lecturers career progression.

Keywords: acceptance, lecturers, open educational resources, knowledge sharing

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Authors: Ben Khayut, Lina Fabri, Maya Avikhana

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The models of the modern Artificial Narrow Intelligence (ANI) cannot: a) independently and continuously function without of human intelligence, used for retraining and reprogramming the ANI’s models, and b) think, understand, be conscious, cognize, infer, and more in state of Uncertainty, and changes in situations, and environmental objects. To eliminate these shortcomings and build a new generation of Artificial Intelligence systems, the paper proposes a Conception, Model, and Method of Computational Psycholinguistic Cognitive Situational-Fuzzy Self-Controlled Brain and Mind System (CPCSFSCBMSUU) using a neural network as its computational memory, operating under uncertainty, and activating its functions by perception, identification of real objects, fuzzy situational control, forming images of these objects, modeling their psychological, linguistic, cognitive, and neural values of properties and features, the meanings of which are identified, interpreted, generated, and formed taking into account the identified subject area, using the data, information, knowledge, and images, accumulated in the Memory. The functioning of the CPCSFSCBMSUU is carried out by its subsystems of the: fuzzy situational control of all processes, computational perception, identifying of reactions and actions, Psycholinguistic Cognitive Fuzzy Logical Inference, Decision making, Reasoning, Systems Thinking, Planning, Awareness, Consciousness, Cognition, Intuition, Wisdom, analysis and processing of the psycholinguistic, subject, visual, signal, sound and other objects, accumulation and using the data, information and knowledge in the Memory, communication, and interaction with other computing systems, robots and humans in order of solving the joint tasks. To investigate the functional processes of the proposed system, the principles of Situational Control, Fuzzy Logic, Psycholinguistics, Informatics, and modern possibilities of Data Science were applied. The proposed self-controlled System of Brain and Mind is oriented on use as a plug-in in multilingual subject Applications.

Keywords: computational brain, mind, psycholinguistic, system, under uncertainty

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Authors: Sima Modirkhameneh, Mohammad Mohammadpanah

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In the process of EFL teachers’ development, self-led reflection (SLR) is thought to have an imperative role because it may help teachers analyze, evaluate, and contemplate what is happening in their classes. Such contemplations can not only enhance the quality of their instruction and provide better learning environments for learners but also improve the quality of their classroom management (CM). Accordingly, understanding the effect of teachers’ SLR practices may help us gain valuable insights into what possible modifications SLR may bring about in all aspects of EFL teachers' practitioners, especially their CM. The main purpose of this case study was, thus, to investigate the impact of SLR practices of 12 Iranian EFL teachers on their CM based on the universal classroom management checklist (UCMC). In addition, another objective of the current study was to have a clear image of EFL teachers’ perceptions of their own SLR practices and their possible outcomes. By conducting repeated reflective interviews, observations, and feedback of the participants over five teaching sessions, the researcher analyzed the outcomes qualitatively through the process of meaning categorization and data interpretation based on the principles of Grounded Theory. The results demonstrated that EFL teachers utilized SLR practices to improve different aspects of their language teaching skills and CM in different contexts. Almost all participants had positive comments and reactions about the effect of SLR on their CM procedures in different aspects (expectations and routines, behavior-specific praise, error corrections, prompts and precorrections, opportunity to respond, strengths and weaknesses of CM, teachers’ perception, CM ability, and learning process). Otherwise stated, results implied that familiarity with the UCMC criteria and reflective practices contributes to modifying teacher participants’ perceptions about their CM procedure and utilizing the reflective practices in their teaching styles. The results are thought to be valuably beneficial for teachers, teacher educators, and policymakers, who are recommended to pay special attention to the contributions as well as the complexity of reflective teaching. The study concludes with more detailed results and implications and useful directions for future research.

Keywords: classroom management, EFL teachers, reflective practices, self-led reflection

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Authors: Ziyad S. Haidar

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Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation

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