Search results for: personalized therapeutic process

Authors: Walid Chakroun, Sorour Alotaibi, Nesreen Ghaddar, Kamel Ghali

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This study aims at determining the extent to which occupant control of microenvironment influences, improves thermal sensation and comfort, and saves energy in spaces equipped with ceiling personalized ventilation (CPV) system assisted by chair fans (CF) and desk fans (DF) in 2 experiments in a climatic chamber equipped with two-station CPV systems, one that allows control of fan flow rate and the other is set to the fan speed of the selected participant in control. Each experiment included two participants each entering the cooled space from transitional environment at a conventional mixed ventilation (MV) at 24 °C. For CPV diffuser, fresh air was delivered at a rate of 20 Cubic feet per minute (CFM) and a temperature of 16 °C while the recirculated air was delivered at the same temperature but at a flow rate 150 CFM. The macroclimate air of the space was at 26 °C. The full speed flow rates for both the CFs and DFs were at 5 CFM and 20 CFM, respectively. Occupant 1 was allowed to operate the CFs or the DFs at (1/3 of the full speed, 2/3 of the full speed, and the full speed) while occupant 2 had no control on the fan speed and their fan speed was selected by occupant 1. Furthermore, a parametric study was conducted to study the effect of increasing the fresh air flow rate on the occupants’ thermal comfort and whole body sensations. The results showed that most occupants in the CPV+CFs, who did not control the CF flow rate, felt comfortable 6 minutes. The participants, who controlled the CF speeds, felt comfortable in around 24 minutes because they were preoccupied with the CFs. For the DF speed control experiments, most participants who did not control the DFs felt comfortable within the first 8 minutes. Similarly to the CPV+CFs, the participants who controlled the DF flow rates felt comfortable at around 26 minutes. When the CPV system was either supported by CFs or DFs, 93% of participants in both cases reached thermal comfort. Participants in the parametric study felt more comfortable when the fresh air flow rate was low, and felt cold when as the flow rate increased.

Keywords: PMV, thermal comfort, thermal environment, thermal sensation

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Authors: Marcio Emilio Dos Santos, Kelly C. F. Dos Santos

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Caregivers of patients diagnosed with ASD are subjected to high stress situations due to the complexity and multiple levels of daily activities that require the organization of events, behaviors and socioemotional situations, such as immediate decision making and in public spaces. The cognitive and emotional requirement needed to fulfill this caregiving role exceeds the regular cultural process that adults receive in their process of preparation for conjugal and parental life. Therefore, in many cases, caregivers present a high level of overload, poor capacity to organize and mediate the development process of the child or patient about their care. Aims: Improvement in the cognitive and emotional capacities related to the caregiver function, allowing the reduction of the overload, the feeling of incompetence and the characteristic level of stress, developing a more organized conduct and decision making more oriented towards the objectives and procedural gains necessary for the integral development of the patient with diagnosis of ASD. Method: The study was performed with 20 relatives, randomly selected from a total of 140 patients attended. The family members were submitted to the Wechsler Adult Intelligence Scale III intelligence test and the Family assessment Management Measure (FaMM) questionnaire as a previous evaluation. Therapeutic activity in a small group of family members or caregivers, with weekly frequency, with a minimum workload of two hours, using the Feuerstein Instrumental Enrichment Cognitive Development Program - Feuerstein Instrumental Enrichment for ten months. Reapplication of the previous tests to verify the gains obtained. Results and Discussion: There is a change in the level of caregiver overload, improvement in the results of the Family assessment Management Measure and highlight to the increase of performance in the cognitive aspects related to problem solving, planned behavior and management of behavioral crises. These results lead to the discussion of the need to invest in the integrated care of patients and their caregivers, mainly by enabling cognitively to deal with the complexity of Autism. This goes beyond the simple therapeutic orientation about adjustments in family and school routines. The study showed that when the caregiver improves his/her capacity of management, the results of the treatment are potentiated and there is a reduction of the level of the caregiver's overload. Importantly, the study was performed for only ten months and the number of family members attended in the study (n = 20) needs to be expanded to have statistical strength.

Keywords: caregiver overload, cognitive development program ASD caregivers, feuerstein instrumental enrichment, family assessment management measure

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Authors: Aratrika Sarkar, Jayita Guha Niyogi

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This paper focuses on the application of general healing design theories to modulate them into case-specific and contextual design considerations. Existing literature focuses on the relationship between architecture and mental health. Primary case studies are selected in India to focus on the effect of a specific location on design considerations. They are qualitatively analysed to further contextualise the inferences from the literature study. An academic project is cited as an example to apply the learnings from the study and understand the influence of various parameters on the design process for further conclusion. Literature studies, case studies and hypothetical design applications helped in finding the different ways of achieving the similar goal of a sensitive approach toward mental health. Along with salutogenic parameters, category of establishment, age group, location of the site and user preference plays a crucial role in the design process. Design of mental health establishments, especially in India, has to involve transparency between stakeholders and users. Owing to different climatic zones and diverse sociocultural traditions, the approach toward healing should adapt accordingly. It should be an effort towards striking a balance between contradictory elements of healing design and resolving the dilemmas with sensitivity and consensus. Lastly, the design should not force a person towards communication or companionship but rather let the person realise that naturally through the healing process.

Keywords: contextual healing design, deinstitutionalisation, Indian mental healthcare establishments, environmental psychology, salutogenesis, therapeutic design

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Authors: Murray Anderson, Galina Freed, Karli Jahn

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Trauma is increasingly recognized as an important construct that has health implications for those who struggle with various mental health issues. For those individuals who meet the criteria for a diagnosis of hoarding disorder (HD), many have experienced some form of trauma. Further, some of the therapeutic interventions for those with HD can further perpetuate or magnify the experience of trauma. Therefore, the aim of this scoping review is to identify and document the nature and extent of research evidence related to trauma as it connects with HD. This review was guided by the questions, ‘How can our understanding of the trauma cycle help us to better appreciate the experiences of individuals who hoard, and how will a trauma informed lens inform the interventions for hoarding disorder? A comprehensive literature search was performed to identify original studies that contained the words “hoarding” and “trauma.” PsychINFO”,''EBSCO host,” “CINAHL” and “PubMed” were searched between January 2005 and April 2021. Articles were screened by three reviewers. Data extracted included publication date, demographics, study design, type of analysis, and noted connections between hoarding and trauma. Of the 329 articles, all duplicates, articles on hoardings of animals, articles not in English, and those without full-text availability were removed. Five categories were found in the remaining 45 articles, including (a) traumatic and stressful life events; (b) the link between posttraumatic stress disorder, trauma, and hoarding; (c) the relationships between different comorbidities, trauma, and hoarding; (d) the lack of early emotional expression and other forms of parental deprivation; and (e) the role of attachment. Lastly, the literature explains how the links between hoarding and trauma are difficult to study due to the highly stigmatized identities with this population. The review provided strong support for the connections between the experience of trauma and HD. What is missing from the literature is the use of a trauma-informed lens to better account for the ways in which hoarding disorder is understood. Other missing pieces in the literature are the potential uses of a trauma-informed lens to enhance the therapeutic process, to understand and reduce treatment attrition, and to improve treatment outcomes. The application of a trauma informed lens could improve our understanding of effective interactions among clients, families, and communities and improve the education around hoarding-related matters. Exploring the connections between trauma and HD can improve therapeutic delivery and destigmatize the experience of dealing with clutter and hoarding concerns. This awareness can also provide health care professionals with both the language and skills to liberate them from a reductionist view on HD.

Keywords: hoarding, attachment, parental deprivation, trauma

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Authors: Matthew I. Bellgard

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The field of bioinformatics has made, and continues to make, substantial progress and contributions to life science research and development. However, this paper contends that a systems approach integrates bioinformatics activities for any project in a defined manner. The application of critical control points in this bioinformatics systems approach may be useful to identify and evaluate points in a pathway where specified activity risk can be reduced, monitored and quality enhanced.

Keywords: bioinformatics, food security, personalized medicine, systems approach

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Authors: Evmorfia Koukia, Polyxeni Mangoulia

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Workshops tend to be a vivid and productive way as an in vivo teaching method. Due to the pandemic, COVID-19 university courses were conducted through the internet. Method It was tried for the first time to integrate online art therapy workshops in a core course named “Special Themes of Mental Health Nursing” in a MSc Program in Mental Health. The duration of the course is 3-hours per week for 11 weeks in a single semester. The course has a main instructor, a professor of psychiatric nursing experienced in arts therapies workshops and visiting art therapists. All art therapists were given a certain topic to cover. Students were encouraged to keep a logbook that was evaluated at the end of the semester and was submitted as a part of the examination process of the course. An interview of 10 minutes was conducted with each student at the end of the course from an independent investigator (an assistant professor) Participants The students (sample) of the program were: nurses, psychologists, and social workers Results: All students who participated in the courses found that the learning process was vivid, encouraging participation and self-motivation, and there were no main differences from in vivo learning. The students identified their personal needs, and they felt a personal connection with the learning experience. The result of the personalized learning was that students discovered their strengths and weaknesses and developed skills like critical thinking. All students admitted that the workshops were the optimal way for them to comprehend the courses’ content, their capability to become therapists, as well as their obstacles and weaknesses while working with patients in mental health. Conclusion: There were no important differences between the views of students in online and in vivo teaching method of the workshops. The result has shown that workshops in mental health can contribute equally in the learning experience.

Keywords: mental health, workshops, students, nursing

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Authors: K. B. Chathyushya, M. Shiva Prakash, R. Hemalatha

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Introduction: Gastrointestinal (GI) tract has a number of microorganisms (microbiota) that influences the host’s health. The imbalance in the gut microbiota, which is also called as gut dysbiosis, affects human health which causes various metabolic, inflammatory, and infectious diseases. Probiotics play an important role in reinstating the gut balance. Probiotics are involved in the maintenance of healthier gut microbiota and have also been identified as effective adjuvants in insulin resistance therapies. Methods: This paper systematically reviews different randomized, controlled, blinded trials of probiotics for the treatment of various diseases along with the therapeutic or prophylactic properties of probiotic bacteria in different metabolic, inflammatory, infectious and anxiety-related disorders. Conclusion: The present review summarises that probiotics have some considerable effect in the management of various diseases, however, the benefits are strain specific, although more clinical trials are need to be carried out with different probiotic and symbiotic combinations as some probiotics have broad spectrum of benefits and few with specific activity

Keywords: life style diseases, cognition, health, gut dysbiosis, probiotics

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Authors: Dong Tran, Thanh Dac Van, Ly Le

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Hemagglutinin (HA) and Neuraminidase (NA) play an important role in host immune evasion across influenza virus evolution process. The correlation between HA and NA evolution in respect to epitopic evolution and drug interaction has yet to be investigated. In this study, combining of sequence to structure evolution and statistical analysis on epitopic/binding site specificity, we identified potential therapeutic features of HA and NA that show specific antibody binding site of HA and specific binding distribution within NA active site of current inhibitors. Our approach introduces the use of sequence variation and molecular interaction to provide an effective strategy in establishing experimental based distributed representations of protein-protein/ligand complexes. The most important advantage of our method is that it does not require complete dataset of complexes but rather directly inferring feature interaction from sequence variation and molecular interaction. Using correlated sequence analysis, we additionally identified co-evolved mutations associated with maintaining HA/NA structural and functional variability toward immunity and therapeutic treatment. Our investigation on the HA binding specificity revealed unique conserved stalk domain interacts with unique loop domain of universal antibodies (CR9114, CT149, CR8043, CR8020, F16v3, CR6261, F10). On the other hand, NA inhibitors (Oseltamivir, Zaninamivir, Laninamivir) showed specific conserved residue contribution and similar to that of NA substrate (sialic acid) which can be exploited for drug design. Our study provides an important insight into rational design and identification of novel therapeutics targeting universally recognized feature of influenza HA/NA.

Keywords: influenza virus, hemagglutinin (HA), neuraminidase (NA), sequence evolution

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Authors: Ren-Jy Ben, Jo-Chi Jao, Chiu-Ya Liao, Ya-Ru Tsai, Lain-Chyr Hwang, Po-Chou Chen

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Cancer is still one of the serious diseases threatening the lives of human beings. How to have an early diagnosis and effective treatment for tumors is a very important issue. The animal carcinoma model can provide a simulation tool for the study of pathogenesis, biological characteristics and therapeutic effects. Recently, drug delivery systems have been rapidly developed to effectively improve the therapeutic effects. Liposome plays an increasingly important role in clinical diagnosis and therapy for delivering a pharmaceutic or contrast agent to the targeted sites. Liposome can be absorbed and excreted by the human body, and is well known that no harm to the human body. This study aimed to compare the therapeutic effects between encapsulated (doxorubicin liposomal, LipoDox) and un-encapsulated (doxorubicin, Dox) anti-tumor drugs using Magnetic Resonance Imaging (MRI). Twenty-four New Zealand rabbits implanted with VX2 carcinoma at left thigh were classified into three groups: control group (untreated), Dox-treated group and LipoDox-treated group, 8 rabbits for each group. MRI scans were performed three days after tumor implantation. A 1.5T GE Signa HDxt whole body MRI scanner with a high resolution knee coil was used in this study. After a 3-plane localizer scan was performed, Three-Dimensional (3D) Fast Spin Echo (FSE) T2-Weighted Images (T2WI) was used for tumor volumetric quantification. And Two-Dimensional (2D) spoiled gradient recalled echo (SPGR) dynamic Contrast-enhanced (DCE) MRI was used for tumor perfusion evaluation. DCE-MRI was designed to acquire four baseline images, followed by contrast agent Gd-DOTA injection through the ear vein of rabbits. Afterwards, a series of 32 images were acquired to observe the signals change over time in the tumor and muscle. The MRI scanning was scheduled on a weekly basis for a period of four weeks to observe the tumor progression longitudinally. The Dox and LipoDox treatments were prescribed 3 times in the first week immediately after VX2 tumor implantation. ImageJ was used to quantitate tumor volume and time course signal enhancement on DCE images. The changes of tumor size showed that the growth of VX2 tumors was effectively inhibited for both LipoDox-treated and Dox-treated groups. Furthermore, the tumor volume of LipoDox-treated group was significantly lower than that of Dox-treated group, which implies that LipoDox has better therapeutic effect than Dox. The signal intensity of LipoDox-treated group is significantly lower than that of the other two groups, which implies that targeted therapeutic drug remained in the tumor tissue. This study provides a radiation-free and non-invasive MRI method for therapeutic monitoring of targeted liposome on an animal tumor model.

Keywords: doxorubicin, dynamic contrast-enhanced MRI, lipodox, magnetic resonance imaging, VX2 tumor model

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Authors: Ljubica Milanović Glavan

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Because of the increasing business pressures, companies must be adaptable and flexible in order to withstand them. Inadequate business processes and low level of business process orientation, that in its core accentuates business processes as opposed to business functions and focuses on process performance and customer satisfaction, hider the ability to adapt to changing environment. It has been shown in previous studies that the companies which have reached higher business process maturity level consistently outperform those that have not reached them. The aim of this paper is to provide a basic understanding of business process orientation concept and business process maturity model. Besides that the paper presents the state of business process orientation in Croatia that has been captured with a study conducted in 2013. Based on the results some practical implications and guidelines for managers are given.

Keywords: business process orientation, business process maturity, Croatia, maturity score

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Authors: Samir Kumar Pal

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Background: Targeted rapid degradation of bilirubin has the potential to thwart incipient bilirubin encephalopathy. Uncontrolled hyperbilirubinemia is a potential problem in developing countries, including India, because of the lack of reliable healthcare institutes for conventional phototherapy. In India, most of the rural subjects duel in the exchange limit during transport, leading to a risk of kernicterus when they arrive at the treatment centre. Thus, an alternative pharmaceutical agent is needed for the hours. Objective: Exploration of a distinct therapeutic strategy for the control of neonatal hyperbilirubinemia compared to conventional phototherapy in a clinical setting. Method: We synthesized, characterized and investigated a spinel-structured Manganese citrate nanocomplex (C-Mn₃O₄ NC, the nanodrug) along with conventional phototherapy in neonatal subjects. We have also observed BIND scores in order to assess neurological dysfunctions. Results: Our observational study clearly reveals that the rate of declination of bilirubin in neonatal subjects with nanodrug oral administration and phototherapy is faster compared to that in the case of phototherapy only. The associated neural dysfunctions were also found to be significantly lower in the case of combined therapy. Conclusion: This study demonstrates that combined therapy works better than conventional phototherapy only for the control of hyperbilirubinemia. We have observed that a significant portion of neonatal subjects requiring blood exchange has been prevented with the combined therapeutic strategy. Further compilation of a drug-safety-dossier is warranted to translate this novel therapeutic chemo preventive approach to clinical settings.

Keywords: nanodrug, nanoparticle, Neonatal hyperbilirubinemia, alternative to phototherapy, redox modulation, redox medicine

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Authors: Mohammad Ehson Rangiha, Bill Karakostas

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Social Business Process Management (SBPM) promises to overcome limitations of traditional BPM by allowing flexible process design and enactment through the involvement of users from a social community. This paper proposes a meta-model and architecture for socially driven business process management systems. It discusses the main facets of the architecture such as goal-based role assignment that combines social recommendations with user profile, and process recommendation, through a real example of a charity organization.

Keywords: business process management, goal-based modelling, process recommendation social collaboration, social BPM

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Authors: Mark Berry

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A number of studies have identified several factors involved in the malignant progression of cancer cells. The Primary modulator in driving inflammation to these transformed cells has been identified as the transcription factor known as nuclear factor-κB. This essential regulator of inflammation and the development of cancer, combined with a microenvironment of inflammation and signaling molecules, plays a major role in the malignant progression of cancer, and this progression is the result of the mutagenic predisposition of persistent substances that combat infection at tumor sites and other areas of chronic inflammation. Inflammation-induced tumors, and their inflammatory cells and regulators may be the primary source of metastasis of tumor cells through angiogenesis. Previous research on cytokines and chemokines, including their downstream targets, has been the focus of the cancer/inflammation connection. The identification of the biological mechanisms of other proteins vital to the inflammation cascade and their interactions are crucial to novel and effective therapeutic protocols for the treatment of inflammation-induced cancers. The Ancelim HSRP Protocol is just such a therapeutic intervention.

Keywords: ancelim, cancer, inflammation, tumor

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Authors: Abigail Tan, Heng Liang Tan, Vanessa Ding, James Hui, Eng Hin Lee, Andre Choo

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Introduction: Comparative oncology investigates the similarities in spontaneous carcinogenesis between humans and animals, in order to identify treatments that can benefit these patients. Companion animals (CA), like canines and felines, are of special interest when it comes to studying human cancers due to their exposure to the same environmental factors and develop tumours with similar features. The purpose of this study is to explore the cross-reactivity of monoclonal antibodies (mAbs) across cancers in humans and CA. Material and Methods: A panel of CA mAbs generated in the lab was screened on multiple human cancer cell lines through flow cytometry to identify for positive binders. Shortlisted candidates were then characterised by biochemical and functional assays e.g., antibody-drug conjugate (ADC) and western blot assays, including glycan studies. Results: Candidate mAb KP52 was generated from whole-cell immunisation using feline mammary carcinoma. KP52 showed strong positive binding to human cancer cells, such as breast cancer and ovarian cancer. Furthermore, KP52 demonstrated strong killing ( > 50%) as an ADC with Saporin as the payload. Western blot results revealed the molecular weight of the antigen targets to be approximately 45kD and 50kD under reduced conditions. Glycan studies suggest that the epitope is glycan in nature, specifically an O-linked glycan. Conclusion: Candidate mAb KP52 has a therapeutic potential as an ADC against feline mammary cancer, human ovarian cancer, human mammary cancer, human pancreatic cancer, and human gastric cancer.

Keywords: ADC, comparative oncology, mAb, therapeutic

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Authors: Joshua Chew, Vesa Cheng, David Thomson

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Background: Hereditary angioedema (HAE) or C1 esterase deficiency is a relatively rare entity that has a potential for significant anesthetic complications. Methods: A literature review was performed of published cases of surgery in patients with HAE. Results were limited to English language only and cases were examined for management strategies and successful prevention of acute attacks. Results: The literature revealed the successful use of C1 esterase inhibitors as the most common agent in surgical prophylaxis therapy. Other therapeutic targets described included kallikrein inhibitors and bradykinin B2 receptor antagonists. Conclusions: Therapeutic targets that exist for the management of acute attacks in HAE have been successfully employed in the setting of surgery. The data is currently limited and could not be used as a firm evidence base, but the limited outcomes seen are positive and reassuring for the prospective anesthetic management of this potentially fatal condition.

Keywords: anesthesia, C1 esterase deficiency, hereditary angioedema, surgical prophylaxis

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Authors: Endrick Barnacin, Jean-Luc Henry, Jimmy Nagau, Jack Molinie

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Being able to identify biological particles such as spores, viruses, or pollens is important for health care professionals, as it allows for appropriate therapeutic management of patients. Optical microscopy is a technology widely used for the analysis of these types of microorganisms, because, compared to other types of microscopy, it is not expensive. The analysis of an optical microscope slide is a tedious and time-consuming task when done manually. However, using machine learning and computer vision, this process can be automated. The first step of an automated microscope slide image analysis process is segmentation. During this step, the biological particles are localized and extracted. Very often, the use of an automatic thresholding method is sufficient to locate and extract the particles. However, in some cases, the particles are not extracted individually because they are stuck to other biological elements. In this paper, we propose a stuck particles separation method based on the use of the Sobel operator and thresholding. We illustrate it by applying it to the separation of 813 images of adjacent pollen grains. The method correctly separated 95.4% of these images.

Keywords: image segmentation, stuck particles separation, Sobel operator, thresholding

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Authors: A. Rahaf, S. Liyakathunsia

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In today’s world, unprecedented operational pressure is faced by banks that test the efficiency, effectiveness, and agility of their business processes. In a typical banking process, a person’s authorization is usually based on his signature on most all of the transactions. Signature verification is considered as one of the highly significant information needed for any bank document processing. Banks usually use Signature Verification to authenticate the identity of individuals. In this paper, a business process model has been proposed in order to increase the quality of the verification process and to reduce time and needed resources. In order to understand the current process, a survey has been conducted and distributed among bank employees. After analyzing the survey, a process model has been created using Bizagi modeler which helps in simulating the process after assigning time and cost of it. The outcomes show that the automation of signature verification process is highly recommended for a banking business process.

Keywords: business process management, process modeling, quality, Signature Verification

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Authors: Agnieszka Stempniewicz, Piotr Ceranowicz, Wojciech Macyk, Jakub Cieszkowski, Beata Kuśnierz-Cabała, Katarzyna Gałązka, Zygmunt Warzecha

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Objectives: There are numerous strategies for the prevention or treatment of oral mucositis. However, their effectiveness is limited and does not correspond to expectations. Recent studies have shown that obestatin exhibits a protective effect and accelerates the healing of gastrointestinal mucosa. The aim of the present study was to examine the influence of obestatin administration on oral ulcers in rats. Methods: lingual ulcers were induced by the use of acetic acid. Rats were treated twice a day intraperitoneally with saline or obestatin(4, 8, or 16 nmol/kg/dose) for five days. The study determined: lingual mucosa morphology, cell proliferation, mucosal blood flow, and mucosal pro-inflammatory interleukin-1β level(IL-1β). Results: In animals without induction of oral ulcers, treatment with obestatin was without any effect. Obestatin administration in rats with lingual ulcers increased the healing rate of these ulcers. Obestatin given at the dose of 8 or 16 nmol/kg/dose caused the strongest and similar therapeutic effect. This result was associated with a significant increase in blood flow and cell proliferation in gingival mucosa, as well as a significant decrease in IL-1β level. Conclusions: Obestatin accelerates the healing of lingual ulcers in rats. This therapeutic effect is well-correlated with an increase in blood flow and cell proliferation in oral mucosa, as well as a decrease in pro-inflammatory IL-1β levels. Obestatin is a potentially useful candidate for the prevention and treatment of oral mucositis. Acknowledgment: Agnieszka Stempniewicz acknowledges the support of InterDokMed project no. POWR.03.02.00- 00-I013/16.

Keywords: oral mucositis, ulcers, obestatin, lingual mucosa

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Authors: Tianjiao Chu, Carla Rios Luci, Christy Maksoudian, Ara Sargsian, Bella B. Manshian, Stefaan J. Soenen

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Nanomaterials have gained high interest in their use as potent anticancer agents. Apart from delivering chemotherapeutic agents in order to reduce off-target effects, molecular agents have also been widely explored. The advances in our understanding of cell biology and cell death mechanisms1 has generated a broad library of potential therapeutic targets by siRNA, mRNA, or pDNA complexes. In the present study, we explore the ability of pDNA-polyplexes to induce tumor-specific necroptosis. This results in a cascade of effects, where immunogenic cell death potentiates anti-tumor immune responses and results in an influx of dendritic cells and cytotoxic T cells, rendering the tumor more amenable to immune checkpoint inhibition. This study aims to explore whether the induction of necroptosis in a subpopulation of tumor cells can be used to potentiate immune checkpoint inhibition studies.

Keywords: nanoparticle, MLKL, necroptosis, immunotherapy

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Authors: Vrushali Guhe, Shailza Singh

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Cutaneous leishmaniasis is neglected tropical disease present worldwide caused by the protozoan parasite Leishmania major, the therapeutic armamentarium for leishmaniasis are showing several limitations as drugs are showing toxic effects with increasing resistance by a parasite. Thus identification of novel therapeutic targets is of paramount importance. Previous studies have shown that autophagy, a cellular process, can either facilitate infection or aid in the elimination of the parasite, depending on the specific parasite species and host background in leishmaniasis. In the present study, our objective was to target the essential autophagy protein ATG8, which plays a crucial role in the survival, infection dynamics, and differentiation of the Leishmania parasite. ATG8 in Leishmania major and its homologue, LC3, in Homo sapiens, act as autophagic markers. Present study manifested the crucial role of ATG8 protein as a potential target for combating Leishmania major infection. Through bioinformatics analysis, we identified non-conserved motifs within the ATG8 protein of Leishmania major, which are not present in LC3 of Homo sapiens. Against these two non-conserved motifs, we generated a peptide library of 60 peptides on the basis of physicochemical properties. These peptides underwent a filtering process based on various parameters, including feasibility of synthesis and purification, compatibility with Selective Reaction Monitoring (SRM)/Multiple reaction monitoring (MRM), hydrophobicity, hydropathy index, average molecular weight (Mw average), monoisotopic molecular weight (Mw monoisotopic), theoretical isoelectric point (pI), and half-life. Further filtering criterion shortlisted three peptides by using molecular docking and molecular dynamics simulations. The direct interaction between ATG8 and the shortlisted peptides was confirmed through Surface Plasmon Resonance (SPR) experiments. Notably, these peptides exhibited the remarkable ability to penetrate the parasite membrane and exert profound effects on Leishmania major. The treatment with these peptides significantly impacted parasite survival, leading to alterations in the cell cycle and morphology. Furthermore, the peptides were found to modulate autophagosome formation, particularly under starved conditions, suggesting their involvement in disrupting the regulation of autophagy within Leishmania major. In vitro, studies demonstrated that the selected peptides effectively reduced the parasite load within infected host cells. Encouragingly, these findings were corroborated by in vivo experiments, which showed a reduction in parasite burden upon peptide administration. Additionally, the peptides were observed to affect the levels of LC3II within host cells. In conclusion, our findings highlight the efficacy of these novel peptides in targeting Leishmania major’s ATG8 and disrupting parasite survival. These results provide valuable insights into the development of innovative therapeutic strategies against leishmaniasis via targeting autophagy protein ATG8 of Leishmania major.

Keywords: ATG8, leishmaniasis, surface plasmon resonance, MD simulation, molecular docking, peptide designing, therapeutics

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Authors: Mohamad F. Jamiluddin, Emeline Sarry, Ana Bejanariu, Cécile Bauche

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Introduction: Over 360 million people are chronically infected with hepatitis B virus (HBV), of whom 1 million die each year from HBV-associated liver cirrhosis or hepatocellular carcinoma. Current treatment options for chronic hepatitis B depend on interferon-α (IFNα) or nucleos(t)ide analogs, which control virus replication but rarely eliminate the virus. Treatment with PEG-IFNα leads to a sustained antiviral response in only one third of patients. After withdrawal of the drugs, the rebound of viremia is observed in the majority of patients. Furthermore, the long-term treatment is subsequently associated with the appearance of drug resistant HBV strains that is often the cause of the therapy failure. Among the new therapeutic avenues being developed, therapeutic vaccine aimed at inducing immune responses similar to those found in resolvers is of growing interest. The high prevalence of chronic hepatitis B necessitates the design of better vaccination strategies capable of eliciting broad-spectrum of cell-mediated immunity(CMI) and humoral immune response that can control chronic hepatitis B. Induction of HBV-specific T cells and B cells by therapeutic vaccination may be an innovative strategy to overcome virus persistence. Lentiviral vectors developed and optimized by THERAVECTYS, due to their ability to transduce non-dividing cells, including dendritic cells, and induce CMI response, have demonstrated their effectiveness as vaccination tools. Method: To develop a HBV therapeutic vaccine that can induce a broad but specific immune response, we generated recombinant lentiviral vector carrying IRES(Internal Ribosome Entry Site)-containing bicistronic constructs which allow the coexpression of two vaccine products, namely HBV T- cell epitope vaccine and HBV virus like particle (VLP) vaccine. HBV T-cell epitope vaccine consists of immunodominant cluster of CD4 and CD8 epitopes with spacer in between them and epitopes are derived from HBV surface protein, HBV core, HBV X and polymerase. While HBV VLP vaccine is a HBV core protein based chimeric VLP with surface protein B-cell epitopes displayed. In order to evaluate the immunogenicity, mice were immunized with lentiviral constructs by intramuscular injection. The T cell and antibody immune responses of the two vaccine products were analyzed using IFN-γ ELISpot assay and ELISA respectively to quantify the adaptive response to HBV antigens. Results: Following a single administration in mice, lentiviral construct elicited robust antigen-specific IFN-γ responses to the encoded antigens. The HBV T- cell epitope vaccine demonstrated significantly higher T cell immunogenicity than HBV VLP vaccine. Importantly, we demonstrated by ELISA that antibodies are induced against both HBV surface protein and HBV core protein when mice injected with vaccine construct (p < 0.05). Conclusion: Our results highlight that THERAVECTYS lentiviral vectors may represent a powerful platform for immunization strategy against chronic hepatitis B. Our data suggests the likely importance of Lentiviral vector based novel bicistronic construct for further study, in combination with drugs or as standalone antigens, as a therapeutic lentiviral based HBV vaccines. THERAVECTYS bicistronic HBV vaccine will be further evaluated in animal efficacy studies.

Keywords: chronic hepatitis B, lentiviral vectors, therapeutic vaccine, virus-like particle

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Authors: Tim J. Walsh, Lindsay E. Young, John A. Schneider

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Background: The disproportionate rate of HIV infection among Black men who have sex with men (BMSM) in the United States suggest the importance of Preexposure Prophylaxis (PrEP) interventions for this population. As such, there is an urgent need for innovative outreach strategies that extend beyond the traditional patient-provider relationship to reach at-risk populations. Training members of the BMSM community as peer change agents (PCAs) is one such strategy. An important piece of this training is goal-setting. Goal-setting not only encourages PCAs to define the parameters of the intervention according to their lived experience, it also helps them plan courses of action. Therefore, the aims of this mixed methods study are: (1) Characterize the goals that BMSM set at the end of their PrEP training and (2) Assess the relationship between goal types and PCA engagement. Methods: Between March 2016 and July 2016, preliminary data were collected from 68 BMSM, ages 18-33, in Chicago as part of an ongoing PrEP intervention. Once enrolled, PCAs participate in a half-day training in which they learn about PrEP, practice initiating conversations about PrEP, and identify strategies for supporting at-risk peers through the PrEP adoption process. Training culminates with a goal-setting exercise, whereby participants establish a goal related to their role as a PCA. Goals were coded for features that either emerged from the data itself or existed in extant goal-setting literature. The main outcomes were (1) number of PrEP conversations PCAs self-report during booster conversations two weeks following the intervention and (2) number of peers PCAs recruit into the study that completed the PrEP workshop. Results: PCA goals (N=68) were characterized in terms of four features: Specificity, target population, personalization, and purpose defined. To date, PCAs report a collective 52 PrEP conversations. 56, 25, and 6% of PrEP conversations occurred with friends, family, and sexual partners, respectively. PCAs with specific goals had more PrEP conversations with at-risk peers compared to those with vague goals (58% vs. 42%); PCAs with personalized goals had more PrEP conversations compared to those with de-personalized goals (60% vs. 53%); and PCAs with goals that defined a purpose had more PrEP conversations compared to those who did not define a purpose (75% vs. 52%). 100% of PCAs with goals that defined a purpose recruited peers into the study compared to 45 percent of PCAs with goals that did not define a purpose. Conclusion: Our preliminary analysis demonstrates that BMSM are motivated to set and work toward a diverse set of goals to support peers in PrEP adoption. PCAs with goals involving a clearly defined purpose had more PrEP conversations and greater peer recruitment than those with goals lacking a defined purpose. This may indicate that PCAs who define their purpose at the outset of their participation will be more engaged in the study than those who do not. Goal-setting may be considered as a component of future HIV prevention interventions to advance intervention goals and as an indicator of PCAs understanding of the intervention.

Keywords: HIV prevention, MSM, peer change agent, preexposure prophylaxis

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Authors: Nitin Dwivedi, Jigna Shah

Abstract:

Brain tumor is metastatic neoplasm of central nervous system, in most of cases it is life threatening disease with low survival rate. Despite of enormous efforts in the development of therapeutics and diagnostic tools, the treatment of brain tumors and gliomas remain a considerable challenge in the area of neuro-oncology. The most reason behind of this the presence of physiological barriers including blood brain barrier and blood brain tumor barrier, lead to insufficient reach ability of therapeutic agents at the site of tumor, result of inadequate destruction of gliomas. So there is an indeed need empowerment of brain tumor imaging for better characterization and delineation of tumors, visualization of malignant tissue during surgery, and tracking of response to chemotherapy and radiotherapy. Multifunctional different generations of dendrimer offer an improved effort for potentiate drug delivery at the site of brain tumor and gliomas. So this article emphasizes the innovative dendrimer approaches in tumor targeting, tumor imaging and delivery of therapeutic agent.

Keywords: blood brain barrier, dendrimer, gliomas, nanotechnology

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Authors: Arslan Masood Pirzada, Muhammad Naeem, Hafiz Haider Ali, Muhammad Latif, Aown Sammar Raza, Asad Hussain Bukhari, Muhammad Saqib, Muhammad Ijaz

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Cyperus rotundus (Cyperaceae), a medicinal herb, is being traditionally used as a home remedy for the treatment of various clinical conditions like diarrhea, diabetic, pyretic, inflammation, malaria, and for treating stomach and bowel disorders. Its current status is one of the most widespread, troublesome, and economically damaging agronomic weeds, growing wildly in various tropical and sub-tropical regions of the world. Tuber and rhizomes of Cyperus rotundus possess a higher concentration of active ingredients in the form of essential oils, phenolic acids, ascorbic acids and flavonoids, responsible for its remedial properties. Exploitation of any medicinal plant application depends on the crucial and comprehensive information about the therapeutic potential of a plant. Researchers have evaluated and characterized the significance of Cyperus rotundus as an anti-androgenic, anti-bacterial, anti-cancerous, anti-convulsant, anti-diabetic, anti-diarrheal, anti-genotoxic, anti-inflammatory, anti-lipidemic, anti-malarial, anti-mutagenic, anti-obesity, anti-oxidant, anti-uropathogenic, hepato-, cardio-, neuroprotective, and nootropic agent. This paper comprises a broad review to summarize the current state of knowledge about chemical constituents, potential economic uses and therapeutic aspects of Cyperus rotundus that will aid in the development of bioethanol and modern herbal medicine through latest technologies that will promote the ability of this plant in the cure of many clinical disorders.

Keywords: purple nutsedge, chemical composition, economic uses, therapeutic values, future directions

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Authors: A. Raj Kumar, A. Okunseinde, P. Raghavan, V. Kapila

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Stroke is the leading cause of adult disability worldwide. With recent advances in immediate post-stroke care, there is an increasing number of young stroke survivors, under the age of 65 years. While most stroke survivors will regain the ability to walk, they often experience long-term arm and hand motor impairments. Long term upper limb rehabilitation is needed to restore movement and function, and prevent deterioration from complications such as learned non-use and learned bad-use. We have developed a novel virtual coach, a wearable instrumented rehabilitation jacket, to motivate individuals to participate in long-term skill re-learning, that can be personalized to their impairment profile. The jacket can estimate the movements of an individual’s arms using embedded off-the-shelf sensors (e.g., 9-DOF IMU for inertial measurements, flex-sensors for measuring angular orientation of fingers) and a Bluetooth Low Energy (BLE) powered microcontroller (e.g., RFduino) to non-intrusively extract data. The 9-DOF IMU sensors contain 3-axis accelerometer, 3-axis gyroscope, and 3-axis magnetometer to compute the quaternions, which are transmitted to a computer to compute the Euler angles and estimate the angular orientation of the arms. The data are used in a gaming environment to provide visual, and/or haptic feedback for goal-based, augmented-reality training to facilitate re-learning in a cost-effective, evidence-based manner. The full paper will elaborate the technical aspects of communication, interactive gaming environment, and physical aspects of electronics necessary to achieve our stated goal. Moreover, the paper will suggest methods to utilize the proposed system as a cheaper, portable, and versatile system vis-à-vis existing instrumentation to facilitate post-stroke personalized arm rehabilitation.

Keywords: feedback, gaming, Euler angles, rehabilitation, augmented reality

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Authors: David E. Culler, Noah D. Anderson

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Integrated systems for product design, manufacturing, and lifecycle management are difficult to implement and customize. Commercial software vendors, including CAD/CAM and third party PDM/PLM developers, create user interfaces and functionality that allow their products to be applied across many industries. The result is that systems become overloaded with functionality, difficult to navigate, and use terminology that is unfamiliar to engineers and production personnel. For example, manufacturers of automotive, aeronautical, electronics, and household products use similar but distinct methods and processes. Furthermore, each company tends to have their own preferred tools and programs for controlling work and information flow and that connect design, planning, and manufacturing processes to business applications. This paper presents a methodology and a case study that addresses these issues and suggests that in the future more companies will develop personalized applications that fit to the natural way that their business operates. A functioning system has been implemented at a highly competitive U.S. aerospace tooling and component supplier that works with many prominent airline manufacturers around the world including The Boeing Company, Airbus, Embraer, and Bombardier Aerospace. During the last three years, the program has produced significant benefits such as the automatic creation and management of component and assembly designs (parametric models and drawings), the extensive use of lightweight 3D data, and changes to the way projects are executed from beginning to end. CATIA (CAD/CAE/CAM) and a variety of programs developed in C#, VB.Net, HTML, and SQL make up the current system. The web-based platform is facilitating collaborative work across multiple sites around the world and improving communications with customers and suppliers. This work demonstrates that the creative use of Application Programming Interface (API) utilities, libraries, and methods is a key to automating many time-consuming tasks and linking applications together.

Keywords: PDM, PLM, collaboration, CAD/CAM, scalable systems

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Authors: Elitaria Bestri Agustina Siregar, Boni Fasius Siregar

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The paper concerned with the transitivity in the reading passage of English textbook for Senior High School. The six types of process were occurred in the passages with percentage as follows: Material Process is 166 (42%), Relational Process is 155 (39%), Mental Process is 39 (10%), Verbal Process is 21 (5%), Existential Process is 13 (3), and Behavioral Process is 5 (1%). The material processes were found to be the most frequently used process type in the samples in our corpus (41,60 %). This indicates that the twenty reading passages are centrally concerned with action and events. Related to developmental psychology theory, this book fits the needs of students of this age.

Keywords: transitivity, types of processes, reading passages, developmental psycholoy

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Authors: Saleit Ron

Abstract:

The Mitar program was established to drive a shift in middle school mathematics education, emphasizing the connection of math to real-life situations, exploring mathematical modeling and literacy, and integrating social and emotional learning (SEL) components for enhanced excellence. The program envisions math coordinators as catalysts for change, equipping them to create educational materials, strengthen leadership skills, and develop SEL competencies within coordinator communities. These skills are then employed to lead transformative efforts within their respective schools. The program engaged 90 participants across six math coordinator communities during 2022-2023, involving 30-60 hours of annual learning. The process includes formative and summative evaluations through questionnaires and interviews, revealing participants' high contentment and successful integration of acquired skills into their schools. Reflections from participants highlighted the need for enhanced change leadership processes, often seeking more personalized mentoring to navigate challenges effectively.

Keywords: math coordinators, mathematical literacy, mathematical modeling, SEL competencies

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Authors: Alex Kiselyov, Suehyun Cho, Darrell Harrington; Florent Cros, Olin Palmer, John Caputo, Michael Kardosh, Eran Oren, William Loudon, Michael Shpigelmacher

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Despite the most aggressive surgical and adjuvant therapeutic strategies, treatment of both pediatric and adult brainstem tumors remains problematic. Novel strategies, including targeted biologics, immunotherapy, and specialized delivery systems such as convection-enhanced delivery (CED), have been proposed. While some of these novel treatments are entering phase I trials, the field is still in need of treatment(s) that exhibits dramatically enhanced potency with optimal therapeutic ratio. Bionaut Labs has developed a modular microrobotic platform for performing localized delivery of diverse therapeutics in vivo. Our biocompatible particles (Bionauts™) are externally propelled and visualized in real-time. Bionauts™ are specifically designed to enhance the effect of radiation therapy via anatomically precise delivery of a radiosensitizing agent, as exemplified by temozolomide (TMZ) and Avastin™ to the brainstem gliomas of diverse origin. The treatment protocol is designed to furnish a better therapeutic outcome due to the localized (vs systemic) delivery of the drug to the neoplastic lesion(s) for use as a synergistic combination of radiation and radiosensitizing agent. In addition, the procedure is minimally invasive and is expected to be appropriate for both adult and pediatric patients. Current progress, including platform optimization, selection of the lead radiosensitizer as well as in vivo safety studies of the Bionauts™ in large animals, specifically the spine and the brain of porcine and ovine models, will be discussed.

Keywords: Bionaut, brainstem, glioma, local delivery, micro-robot, radiosensitizer

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Authors: Helga Martins, Idália Matias

Abstract:

Background:Multiple sclerosis is a chronic inflammatory autoimmune demyelinating disease that affects young adults. Multiple sclerosis is a chronic disease in which the patient needs to self-manage the disease and the therapeutic regimen. Consequently, the promotion of health literacy assumes a relevant role for the accessibility, understanding, and use of information in order to promote and maintain the health of patients with multiple sclerosis. Aim: To determine the impact of lower health literacy in the self-management of patients with a multiple sclerosis. Methods: Literature review based on a search on the following electronic databases: CINAHLand MEDLINE; comprising all results published between September 2016 and September 2021. The search strategy was: (“Self-management [MeSH]” AND “Multiple sclerosis[MeSH]”AND “Health literacy[MeSH]”). The inclusion criteria were: original papers reporting about multiple sclerosis patients; participants with age above 18 years old, written in English, Spanish, French, or Portuguese. Two independent reviewers have done the screening and analysis of the results. 38 citations were identified, and after duplicates removal, a total of 25 results were screened; 14 were included after the application of the inclusion criteria. Results: The lower health literacy in the self-management of patients with a multiple sclerosis is related toless healthy choices, riskier health behavior, poor health outcomes, decreased of adhering to the therapeutic regimen after discharge, less self-management of chronic illness, and increased the time of hospitalization. Conclusion: Inadequate levels of health literacy contribute to poor health outcomes, unsuccessful self-management of chronic illness, and inadequate adherence to the therapeutic regimen. Therefore, health literacy is important for health policy and the healthcare services, as it can be understood as a mediator of self-management of multiple sclerosis disease.

Keywords: health literacy, multiple sclerosis, review, self-management

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