Search results for: digital patient passport

Authors: Asma Ben Hmidene, Mizuho Hanaki, Kazuma Murakami, Kazuhiro Irie, Hiroko Isoda, Hideyuki Shigemori

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Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) are characterized as a peripheral metabolic disorder and a degenerative disease of the central nervous system, respectively. It is now widely recognized that T2DM and AD share many pathophysiological features including glucose metabolism, increased oxidative stress and amyloid aggregation. Amyloid beta (Aβ) is the components of the amyloid deposits in the AD brain and while the component of the amyloidogenic peptide deposit in the pancreatic islets of Langerhans is identified as human islet amyloid polypeptide (hIAPP). These two proteins are originated from the amyloid precursor protein and have a high sequence similarity. Although the amino acid sequences of amyloidogenic proteins are diverse, they all adopt a similar structure in aggregates called cross-beta-spine. Add at that, extensive studies in the past years have found that like Aβ1-42, IAPP forms early intermediate assemblies as spherical oligomers, implicating that these oligomers possess a common folding pattern or conformation. These similarities can be used in the search for effective pharmacotherapy for DM, since potent therapeutic agents such as antioxidants with a catechol moiety, proved to inhibit Aβ aggregation, may play a key role in the inhibit the aggregation of hIAPP treatment of patients with DM. Tamarix gallica is one of the halophyte species having a powerful antioxidant system. Although it was traditionally used for the treatment of various liver metabolic disorders, there is no report about the use of this plant for the treatment or prevention of T2DM and AD. Therefore, the aim of this work is to investigate their protective effect towards T2DM and AD by isolation and identification of α-glucosidase inhibitors, with antioxidant potential, that play an important role in the glucose metabolism in diabetic patient, as well as, the polymerization of hIAPP and Aβ aggregation inhibitors. Structure-activity relationship study was conducted for both assays. And as for α-glucosidase inhibitors, their mechanism of action and their synergistic potential when applied with a very low concentration of acarbose were also suggesting that they can be used not only as α-glucosidase inhibitors but also be combined with established α-glucosidase inhibitors to reduce their adverse effect. The antioxidant potential of the purified substances was evaluated by DPPH and SOD assays. Th-T assay using 42-mer amyloid β-protein (Aβ42) for AD and hIAPP which is a 37-residue peptide secreted by the pancreatic β –cells for T2DM and Transmission electronic microscopy (TEM) were conducted to evaluate the amyloid aggragation of the actives substances. For α-glucosidase, p-NPG and glucose oxidase assays were performed for determining the inhibition potential and structure-activity relationship study. The Enzyme kinetic protocol was used to study the mechanism of action. From this research, it was concluded that polyphenols playing a role in the glucose metabolism and oxidative stress can also inhibit the amyloid aggregation, and that substances with a catechol and glucuronide moieties inhibiting amyloid-β aggregation, might be used to inhibit the aggregation of hIAPP.

Keywords: α-glucosidase inhibitors, amyloid aggregation inhibition, mechanism of action, polyphenols, structure activity relationship, synergistic potential, tamarix gallica

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Authors: Maryam Fallahpoor, Biswajeet Pradhan

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Background: Artificial intelligence (AI) serves as a valuable tool in mitigating the scarcity of human resources required for the evaluation and categorization of vast quantities of medical imaging data. When AI operates with optimal precision, it minimizes the demand for human interpretations and, thereby, reduces the burden on radiologists. Among various AI approaches, deep learning (DL) stands out as it obviates the need for feature extraction, a process that can impede classification, especially with intricate datasets. The advent of DL models has ushered in a new era in medical imaging, particularly in the context of COVID-19 detection. Traditional 2D imaging techniques exhibit limitations when applied to volumetric data, such as Computed Tomography (CT) scans. Medical images predominantly exist in one of two formats: neuroimaging informatics technology initiative (NIfTI) and digital imaging and communications in medicine (DICOM). Purpose: This study aims to employ DL for the classification of COVID-19-infected pulmonary patients and normal cases based on 3D CT scans while investigating the impact of image format. Material and Methods: The dataset used for model training and testing consisted of 1245 patients from IranMehr Hospital. All scans shared a matrix size of 512 × 512, although they exhibited varying slice numbers. Consequently, after loading the DICOM CT scans, image resampling and interpolation were performed to standardize the slice count. All images underwent cropping and resampling, resulting in uniform dimensions of 128 × 128 × 60. Resolution uniformity was achieved through resampling to 1 mm × 1 mm × 1 mm, and image intensities were confined to the range of (−1000, 400) Hounsfield units (HU). For classification purposes, positive pulmonary COVID-19 involvement was designated as 1, while normal images were assigned a value of 0. Subsequently, a U-net-based lung segmentation module was applied to obtain 3D segmented lung regions. The pre-processing stage included normalization, zero-centering, and shuffling. Four distinct 3D CNN models (ResNet152, ResNet50, DensNet169, and DensNet201) were employed in this study. Results: The findings revealed that the segmentation technique yielded superior results for DICOM images, which could be attributed to the potential loss of information during the conversion of original DICOM images to NIFTI format. Notably, ResNet152 and ResNet50 exhibited the highest accuracy at 90.0%, and the same models achieved the best F1 score at 87%. ResNet152 also secured the highest Area under the Curve (AUC) at 0.932. Regarding sensitivity and specificity, DensNet201 achieved the highest values at 93% and 96%, respectively. Conclusion: This study underscores the capacity of deep learning to classify COVID-19 pulmonary involvement using real 3D hospital data. The results underscore the significance of employing DICOM format 3D CT images alongside appropriate pre-processing techniques when training DL models for COVID-19 detection. This approach enhances the accuracy and reliability of diagnostic systems for COVID-19 detection.

Keywords: deep learning, COVID-19 detection, NIFTI format, DICOM format

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Authors: Teresa Rushe, Nicole Devlin, Tara O Neill

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In this study, we sought to examine associations between childhood experiences of community and collective violence and psychological functioning in young people who grew up in post-conflict Northern Ireland. We hypothesized that those who grew up with such experiences would demonstrate internalizing and externalizing difficulties in early adulthood and, furthermore, that these difficulties would be mediated by adverse childhood experiences occurring within the home environment. As part of the Northern Ireland Childhood Adversity Study, we recruited 213 young people aged 18-25 years (108 males) who grew up in the post-conflict society of Northern Ireland using purposive sampling. Participants completed a digital questionnaire to measure adverse childhood experiences as well as aspects of psychological functioning. We employed the Adverse Childhood Experience -International Questionnaire (ACE-IQ¬) adaptation of the original Adverse Childhood Experiences Questionnaire (ACE) as it additionally measured aspects of witnessing community violence (e.g., seeing someone being beaten/killed, fights) and experiences of collective violence (e.g., war, terrorism, police, or gangs’ battles exposure) during the first 18 years of life. 51% of our sample reported experiences of community and/or collective violence (N=108). Compared to young people with no such experiences (N=105), they also reported significantly more adverse experiences indicative of household dysfunction (e.g., family substance misuse, mental illness or domestic violence in the family, incarceration of a family member) but not more experiences of abuse or neglect. As expected, young people who grew up with the community and/or collective violence reported significantly higher anxiety and depression scores and were more likely to engage in acts of deliberate self-harm (internalizing symptoms). They also started drinking and taking drugs at a younger age and were significantly more likely to have been in trouble with the police (externalizing symptoms). When the type of violence exposure was separated by whether the violence was witnessed (community violence) or more directly experienced (collective violence), we found community and collective violence to have similar effects on externalizing symptoms, but for internalizing symptoms, we found evidence of a differential effect. Collective violence was associated with depressive symptoms, whereas witnessing community violence was associated with anxiety-type symptoms and deliberate self-harm. However, when experiences of household dysfunction were entered into the models predicting anxiety, depression, and deliberate self-harm, none of the main effects remained significant. This suggests internalizing type symptoms are mediated by immediate family-level experiences. By contrast, significant community and collective violence effects on externalizing behaviours: younger initiation of alcohol use, younger initiation of drug use, and getting into trouble with the police persisted after controlling for family-level factors and thus are directly associated with growing up with the community and collective violence. Given the cross-sectional nature of our study, we cannot comment on the direction of the effect. However, post-hoc correlational analyses revealed associations between externalising behaviours and personal factors, including greater risk-taking and young age at puberty. The implications of the findings will be discussed in relation to interventions for young people and families living with the community and collective violence.

Keywords: community and collective violence, adverse childhood experiences, youth, psychological wellbeing

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Authors: Saqib Aziz, Brad Alexander, Christoph Gengnagel, Stefan Weinzierl

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This paper explores a generative design, simulation, and optimization workflow for the integration of acoustical diffuser and/or absorber geometry with embedded coupled Helmholtz-resonators for full-scale 3D printed building components. Large-scale additive manufacturing in conjunction with algorithmic CAD design tools enables a vast amount of control when creating geometry. This is advantageous regarding the increasing demands of comfort standards for indoor spaces and the use of more resourceful and sustainable construction methods and materials. The presented methodology highlights these new technological advancements and offers a multimodal and integrative design solution with the potential for an immediate application in the AEC-Industry. In principle, the methodology can be applied to a wide range of structural elements that can be manufactured by additive manufacturing processes. The current paper focuses on a case study of an application for a biaxial load-bearing beam grillage made of reinforced concrete, which allows for a variety of applications through the combination of additive prefabricated semi-finished parts and in-situ concrete supplementation. The semi-prefabricated parts or formwork bodies form the basic framework of the supporting structure and at the same time have acoustic absorption and diffusion properties that are precisely acoustically programmed for the space underneath the structure. To this end, a hybrid validation strategy is being explored using a digital and cross-platform simulation environment, verified with physical prototyping. The iterative workflow starts with the generation of a parametric design model for the acoustical geometry using the algorithmic visual scripting editor Grasshopper3D inside the building information modeling (BIM) software Revit. Various geometric attributes (i.e., bottleneck and cavity dimensions) of the resonator are parameterized and fed to a numerical optimization algorithm which can modify the geometry with the goal of increasing absorption at resonance and increasing the bandwidth of the effective absorption range. Using Rhino.Inside and LiveLink for Revit, the generative model was imported directly into the Multiphysics simulation environment COMSOL. The geometry was further modified and prepared for simulation in a semi-automated process. The incident and scattered pressure fields were simulated from which the surface normal absorption coefficients were calculated. This reciprocal process was repeated to further optimize the geometric parameters. Subsequently the numerical models were compared to a set of 3D concrete printed physical twin models, which were tested in a .25 m x .25 m impedance tube. The empirical results served to improve the starting parameter settings of the initial numerical model. The geometry resulting from the numerical optimization was finally returned to grasshopper for further implementation in an interdisciplinary study.

Keywords: acoustical design, additive manufacturing, computational design, multimodal optimization

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Authors: Nils Haglund, Svenolof Dahlgren, Maria Rastam, Peik Gustafsson, Karin Kalien

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In Sweden, like in most developed countries, there is a substantial increase of children diagnosed with autism and other conditions within the autism spectrum (ASD). The rapid increase of ASD rates stresses the importance of developing care programs to provide support and comprehensive interventions for affected families. The current observational study was conducted in order to evaluate an ongoing Comprehensive Intensive Early Intervention (CIEI) program for children with autism in southern Sweden. The change in autism symptoms among children participating in CIEI (intervention group, n=67) was compared with children who received traditional habilitation services only (comparison group, n=27). Children of parents who accepted the offered CIEI-program, constituted the intervention group, whereas children, whose parents (for some reason) were not interested in the offered CIEI-program, constituted the comparison group. The CIEI-program was individualized to each child by experienced applied behavior analysis (ABA) specialists with different backgrounds as psychologists, speech pathologists or special education teachers, in cooperation with parents and preschool staff. Due to the individualization, the intervention could vary in intensity and techniques. The intensity was calculated to 15-25 hours each week at home and the preschool altogether. Each child was assigned one 'trainer', who was often employed as a preschool teacher but could have another educational background. An agreement between supervisor- parents and preschool staff was reached to confirm the intensity and content of the CIEI- program over an approximately two-year intervention period. Symptom changes were measured as evaluation-ADOS-2-scores, total- and severity-scores, minus the corresponding baseline-scores, divided by the time between baseline and evaluation. The difference between the study-groups regarding change of ADOS-2-scores was estimated using ANCOVA. In the current study, children in the CIEI-group improved their ADOS-2-total scores between baseline and evaluation (-0.8 scores per year; 95%CI: -1.2 to -0.4), whereas no such improvement was detected in the comparison group (+0.1 scores per year; 95%CI: -0.7 to +0.9). The change difference (change in the CIEI-group vs. change in the comparison group) was statistically significant, both crude and after adjusting for possible confounders (-1.1; 95%CI -1.9 to -0.4). Children in the CIEI-group also significantly improved their ADOS-calibrated severity scores, but not significantly differently so from the comparison group. The results from the current study indicate that the CIEI program significantly improves social and communicative skills among children with autism and that children with developmental delay could benefit to a similar degree as other children. The results support earlier studies reporting on the improvement of autism symptoms after early intensive interventions. The results from observational studies are difficult to interpret, but it is nevertheless of uttermost importance to evaluate costly autism intervention programs. Such results may be of immediate importance to healthcare organizations when allocating the already strained resources to different patient groups. Albeit the obvious limitation of the current naturalistic study, the results support previous positive studies and indicate that children with autism benefit from participating in early comprehensive, intensive programs and that investments in these programs may be highly justifiable.

Keywords: autism symptoms, ADOS-scores, evaluation, intervention program

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Authors: Vitaliy Petrov, Natalia Shusharina, Vitaliy Kasymov, Maksim Patrushev, Evgeny Bogdanov

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The leading worldwide death reasons are ischemic heart disease and other cardiovascular illnesses. Generally, the common symptom is high blood pressure. Long-time blood pressure control is very important for the prophylaxis, correct diagnosis and timely therapy. Non-invasive methods which are based on Korotkoff sounds are impossible to apply often and for a long time. Implantable devices can combine longtime monitoring with high accuracy of measurements. The main purpose of this work is to create a real-time monitoring system for decreasing the death rate from cardiovascular diseases. These days implantable electronic devices began to play an important role in medicine. Usually implantable devices consist of a transmitter, powering which could be wireless with a special made battery and measurement circuit. Common problems in making implantable devices are short lifetime of the battery, big size and biocompatibility. In these work, blood pressure measure will be the focus because it’s one of the main symptoms of cardiovascular diseases. Our device will consist of three parts: the implantable pressure sensor, external transmitter and automated workstation in a hospital. The Implantable part of pressure sensors could be based on piezoresistive or capacitive technologies. Both sensors have some advantages and some limitations. The Developed circuit is based on a small capacitive sensor which is made of the technology of microelectromechanical systems (MEMS). The Capacitive sensor can provide high sensitivity, low power consumption and minimum hysteresis compared to the piezoresistive sensor. For this device, it was selected the oscillator-based circuit where frequency depends from the capacitance of sensor hence from capacitance one can calculate pressure. The external device (transmitter) used for wireless charging and signal transmission. Some implant devices for these applications are passive, the external device sends radio wave signal on internal LC circuit device. The external device gets reflected the signal from the implant and from a change of frequency is possible to calculate changing of capacitance and then blood pressure. However, this method has some disadvantages, such as the patient position dependence and static using. Developed implantable device doesn’t have these disadvantages and sends blood pressure data to the external part in real-time. The external device continuously sends information about blood pressure to hospital cloud service for analysis by a physician. Doctor’s automated workstation at the hospital also acts as a dashboard, which displays actual medical data of patients (which require attention) and stores it in cloud service. Usually, critical heart conditions occur few hours before heart attack but the device is able to send an alarm signal to the hospital for an early action of medical service. The system was tested with wireless charging and data transmission. These results can be used for ASIC design for MEMS pressure sensor.

Keywords: MEMS sensor, RF power, wireless data, oscillator-based circuit

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Authors: Josie Gardner

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The overall intention of this research is to reimagine peacebuilding in both in theory and practical application in light of the shortcomings and unsustainability of the current peacebuilding paradigm. These limitations are identified here as an overly rational-material approach to peacebuilding that neglects the inner dimension of peace for a fragmented rather than holistic model, and that espouses a conflict and violence-centric approach to peacebuilding. In counter, this presentation is purposed to investigate the dynamics of inner and outer peace as a holistic, complex system towards ‘inner-outer’ peacebuilding. This paper draws from primary research in the protracted conflict context of north-western India (Jammu, Kashmir & Ladakh) as a case study. This presentation has two central aims. First, to introduce the process of inner (psycho-spiritual) peacebuilding, which has thus far been neglected by mainstream and orthodox literature. Second, to examine why inner peacebuilding is essential for realising sustainable peace on a broader scale as outer (socio-political) peace and to better understand how the inner and outer dynamics of peace relate and affect one another. To these ends, Josephine (the researcher/author/presenter) partnered with Yakjah Reconciliation and Development Network to implement a series of action-oriented workshops and retreats centred around healing, reconciliation, leadership, and personal development for the dual purpose of collaboratively generating data, theory, and insights, as well as providing the youth leaders with an experiential, transformative experience. The research team created and used a novel methodological approach called Mapping Ritual Ecologies, which draws from Participatory Action Research and Digital Ethnography to form a collaborative research model with a group of 20 youth co-researchers who are emerging youth peace leaders in Kashmir, Jammu, and Ladakh. This research found significant intra- and inter-personal shifts towards an experience of inner peace through inner peacebuilding activities. Moreover, this process of inner peacebuilding affected their families and communities through interpersonal healing and peace leadership in an inside-out process of change. These insights have generated rich insights and have supported emerging theories about the dynamics between inner and outer peace, power, justice, and collective healing. This presentation argues that the largely neglected dimension of inner (psycho-spiritual) peacebuilding is imperative for broader socio-political (outer) change. Changing structures of oppression, injustice, and violence—i.e. structures of separation—requires individual, interpersonal, and collective healing. While this presentation primarily examines and advocates for inside-out peacebuilding and social justice, it will also touch upon the effect of systems of separation on the inner condition and human experience. This research reimagines peacebuilding as a holistic inner-outer approach. This offers an alternative path forward those weaves together self-actualisation and social justice. While contextualised within north-western India with a small case study population, the findings speak also to other conflict contexts as well as our global peacebuilding and social justice milieu.

Keywords: holistic, inner peacebuilding, psycho-spiritual, systems youth

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Authors: J. S. M. Yang, G. E. T. Chua

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Diploma in Optometry (OPT) course is a three-year program offered by Ngee Ann Polytechnic (NP) to train students to provide primary eye care. Students are equipped with foundational conceptual knowledge and practical skills in the first three semesters before clinical modules in fourth to six semesters. In the clinical modules, students typically have difficulties in integrating the acquired knowledge and skills from the past semesters to perform general eye examinations on public patients at NP Optometry Centre (NPOC). To help the students overcome the challenge, a web-based game Virtual Optometrist (VO) was developed to help students apply their skills and knowledge through scenario-based learning. It consisted of two interfaces, Optical Practice Counter (OPC) and Optometric Consultation Room (OCR), to provide two simulated settings for authentic learning experiences. In OPC, students would recommend and provide appropriate frame and lens selection based on virtual patient’s case history. In OCR, students would diagnose and manage virtual patients with common ocular conditions. Simulated scenarios provided real-world clinical situations that required contextual application of integrated knowledge from relevant modules. The stages in OPC and OCR are of increasing complexity to align to expected students’ clinical competency as they progress to more senior semesters. This prevented gameplay fatigue as VO was used over the semesters to achieve different learning outcomes. Numerous feedback opportunities were provided to students based on their decisions to allow individualized learning to take place. The game-based learning element in VO was achieved through the scoreboard and leader board to enhance students' motivation to perform. Scores were based on the speed and accuracy of students’ responses to the questions posed in the simulated scenarios, preparing the students to perform accurately and effectively under time pressure in a realistic optometric environment. Learning analytics was generated in VO’s backend office based on students’ responses, offering real-time data on distinctive and observable learners’ behavior to monitor students’ engagement and learning progress. The backend office allowed versatility to add, edit, and delete scenarios for different intended learning outcomes. Likert Scale was used to measure students’ learning experience with VO for OPT Year 2 and 3 students. The survey results highlighted the learning benefits of implementing VO in the different modules, such as enhancing recall and reinforcement of clinical knowledge for contextual application to develop higher-order thinking skills, increasing efficiency in clinical decision-making, facilitating learning through immediate feedback and second attempts, providing exposure to common and significant ocular conditions, and training effective communication skills. The results showed that VO has been useful in reinforcing optometry students’ learning and supporting the development of higher-order thinking, increasing efficiency in clinical decision-making, and allowing students to learn from their mistakes with immediate feedback and second attempts. VO also exposed the students to diverse ocular conditions through simulated real-world clinical scenarios, which may otherwise not be encountered in NPOC, and promoted effective communication skills.

Keywords: authentic learning, game-based learning, scenario-based learning, simulated clinical scenarios

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Authors: Lucas M. Furlan, Cesar A. Moreira, Jepherson F. Sales, Guilherme T. Bueno, Manuel E. Ferreira, Carla V. S. Coelho, Vania Rosolen

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Located in the western part of the State of Minas Gerais, Brazil, the study area consists of a savanna environment, represented by sedimentary plateau and a soil cover composed by lateritic and hydromorphic soils - in the latter, occurring the deferruginization and concentration of high-alumina clays, exploited as refractory material. In the hydromorphic topographic depressions (wetlands) the hydropedogical relationships are little known, but it is observed that in times of rainfall, the depressed region behaves like a natural seasonal reservoir - which suggests that the wetlands on the surface of the plateau are places of recharge of the aquifer. The aquifer recharge areas are extremely important for the sustainable social, economic and environmental development of societies. The understanding of hydrodynamics in relation to the functioning of the ferruginous and hydromorphic lateritic soils system in the savanna environment is a subject rarely explored in the literature, especially its understanding through the joint application of geoprocessing by UAV (Unmanned Aerial Vehicle) and electrical tomography. The objective of this work is to understand the hydrogeological dynamics in a wetland (with an area of 426.064 m²), in the Brazilian savanna,as well as the understanding of the subsurface architecture of hydromorphic depressions in relation to the recharge of aquifers. The wetland was compartmentalized in three different regions, according to the geoprocessing. Hydraulic conductivity studies were performed in each of these three portions. Electrical tomography was performed on 9 lines of 80 meters in length and spaced 10 meters apart (direction N45), and a line with 80 meters perpendicular to all others. With the data, it was possible to generate a 3D cube. The integrated analysis showed that the area behaves like a natural seasonal reservoir in the months of greater precipitation (December – 289mm; January – 277,9mm; February – 213,2mm), because the hydraulic conductivity is very low in all areas. In the aerial images, geotag correction of the images was performed, that is, the correction of the coordinates of the images by means of the corrected coordinates of the Positioning by Precision Point of the Brazilian Institute of Geography and Statistics (IBGE-PPP). Later, the orthomosaic and the digital surface model (DSM) were generated, which with specific geoprocessing generated the volume of water that the wetland can contain - 780,922m³ in total, 265,205m³ in the region with intermediate flooding and 49,140m³ in the central region, where a greater accumulation of water was observed. Through the electrical tomography it was possible to identify that up to the depth of 6 meters the water infiltrates vertically in the central region. From the 8 meters depth, the water encounters a more resistive layer and the infiltration begins to occur horizontally - tending to concentrate the recharge of the aquifer to the northeast and southwest of the wetland. The hydrodynamics of the area is complex and has many challenges in its understanding. The next step is to relate hydrodynamics to the evolution of the landscape, with the enrichment of high-alumina clays, and to propose a management model for the seasonal reservoir.

Keywords: electrical tomography, hydropedology, unmanned aerial vehicle, water resources management

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Authors: Li Jiuen Ong, Magdalin Cheong, Sri Rahayu, Lek Alexander, Pei Ting Tan

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Background: Previous programme evaluations from the diabetes training programme conducted in Changi General Hospital revealed that healthcare professionals (HCPs) are keen to receive advance diabetes training and education, specifically in medical, nutritional therapy. HCPs also expressed a preference for interactive activities over didactic teaching methods to enhance their learning. Since the War on Diabetes was initiated by MOH in 2016, HCPs are challenged to be actively involved in continuous education to be better equipped to reduce the growing burden of diabetes. Hence, streamlining training to incorporate an element of fun is of utmost importance. Aim: The nutrition programme incorporates game play using an interactive board game that aims to provide a more conducive and less stressful environment for learning. The board game could be adapted for training of community HCPs, health ambassadors or caregivers to cope with the increasing demand of diabetes care in the hospital and community setting. Methodology: Stages for game’s conception (Jaffe, 2001) were adopted in the development of the interactive board game ‘Sweet Score™ ’ Nutrition concepts and topics in diabetes self-management are embedded into the game elements of varying levels of difficulty (‘Easy,’ ‘Medium,’ ‘Hard’) including activities such as a) Drawing/ sculpting (Pictionary-like) b)Facts/ Knowledge (MCQs/ True or False) Word definition) c) Performing/ Charades To study the effects of game play on knowledge acquisition and perceived experiences, participants were randomised into two groups, i.e., lecture group (control) and game group (intervention), to test the difference. Results: Participants in both groups (control group, n= 14; intervention group, n= 13) attempted a pre and post workshop quiz to assess the effectiveness of knowledge acquisition. The scores were analysed using paired T-test. There was an improvement of quiz scores after attending the game play (mean difference: 4.3, SD: 2.0, P<0.001) and the lecture (mean difference: 3.4, SD: 2.1, P<0.001). However, there was no significance difference in the improvement of quiz scores between gameplay and lecture (mean difference: 0.9, 95%CI: -0.8 to 2.5, P=0.280). This suggests that gameplay may be as effective as a lecture in terms of knowledge transfer. All the13 HCPs who participated in the game rated 4 out of 5 on the likert scale for the favourable learning experience and relevance of learning to their job, whereas only 8 out of 14 HCPs in the lecture reported a high rating in both aspects. 16. Conclusion: There is no known board game currently designed for diabetes training for HCPs.Evaluative data from future training can provide insights and direction to improve the game format and cover other aspects of diabetes management such as self-care, exercise, medications and insulin management. Further testing of the board game to ensure learning objectives are met is important and can assist in the development of awell-designed digital game as an alternative training approach during the COVID-19 pandemic. Learning through gameplay increases opportunities for HCPs to bond, interact and learn through games in a relaxed social setting and potentially brings more joy to the workplace.

Keywords: active learning, game, diabetes, nutrition

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Authors: Javier Enciso-Benavides, Fredy Fabian, Carlos Castaneda, Luis Alfaro, Alex Choque, Aparicio Aguilar, Javier Enciso

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Background: The use of biomarkers in breast cancer diagnosis, therapy, and prognosis has gained increasing interest. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and may cause relapse. Therefore, due to the importance of diagnosis, therapy, and prognosis, several biomarkers that characterize CSCs have been identified; however, in treatment-naïve triple-negative breast tumors, there is an urgent need to identify new biomarkers and therapeutic targets. According to this, the aim of this study was to identify serum proteins associated with cancer stem cells and pluripotency in women with triple-negative breast tumors in order to subsequently identify a biomarker for this type of breast tumor. Material and Methods: Whole blood samples from 12 women with histopathologically diagnosed triple-negative breast tumors were used after obtaining informed consent from the patient. Blood serum was obtained by conventional procedure and frozen at -80ºC. Identification of cancer stem cell-associated proteins was performed by matrix-assisted laser desorption/ionisation-assisted laser desorption/ionisation mass spectrometry (MALDI-TOF MS), protein analysis was obtained using the AB Sciex TOF/TOF™ 5800 system (AB Sciex, USA). Sequences not aligned by ProteinPilot™ software were analyzed by Protein BLAST. Results: The following proteins related to pluripotency and cancer stem cells were identified by MALDI TOF/TOF mass spectrometry: A-chain, Serpin A12 [Homo sapiens], AIEBP [Homo sapiens], Alpha-one antitrypsin, AT {internal fragment} [human, partial peptide, 20 aa] [Homo sapiens], collagen alpha 1 chain precursor variant [Homo sapiens], retinoblastoma-associated protein variant [Homo sapiens], insulin receptor, CRA_c isoform [Homo sapiens], Hydroxyisourate hydrolase [Streptomyces scopuliridis], MUCIN-6 [Macaca mulatta], Alpha-actinin-3 [Chrysochloris asiatica], Polyprotein M, CRA_d isoform, partial [Homo sapiens], Transcription factor SOX-12 [Homo sapiens]. Recommendations: The serum proteins identified in this study should be investigated in the exosome of triple-negative breast cancer stem cells and in the blood serum of women without breast cancer. Subsequently, proteins found only in the blood serum of women with triple-negative breast cancer should be identified in situ in triple-negative breast cancer tissue in order to identify a biomarker to study the evolution of this type of cancer, or that could be a therapeutic target. Conclusions: Eleven cancer stem cell-related serum proteins were identified in 12 women with triple-negative breast cancer, of which MUCIN-6, retinoblastoma-associated protein variant, transcription factor SOX-12, and collagen alpha 1 chain are the most representative and have not been studied so far in this type of breast tumor. Acknowledgement: This work was supported by Proyecto CONCYTEC–Banco Mundial “Mejoramiento y Ampliacion de los Servicios del Sistema Nacional de Ciencia Tecnología e Innovacion Tecnologica” 8682-PE (104-2018-FONDECYT-BM-IADT-AV).

Keywords: triple-negative breast cancer, MALDI TOF/TOF MS, serum proteins, cancer stem cells

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Authors: Andy Alubaidy

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In this work, a robotic additive manufacturing system (RAMS) that is capable of three-dimensional (3D) printing in six degrees of freedom (DOF) with very high accuracy and virtually on any surface has been designed and built. One of the major shortcomings in existing 3D printer technology is the limitation to three DOF, which results in prolonged fabrication time. Depending on the techniques used, it usually takes at least two hours to print small objects and several hours for larger objects. Another drawback is the size of the printed objects, which is constrained by the physical dimensions of most low-cost 3D printers, which are typically small. In such cases, large objects are produced by dividing them into smaller components that fit the printer’s workable area. They are then glued, bonded or otherwise attached to create the required object. Another shortcoming is material constraints and the need to fabricate a single part using different materials. With the flexibility of a six-DOF robot, the RAMS has been designed to overcome these problems. A feeding mechanism using an adaptive Proportional-Integral-Derivative (PID) controller is utilized along with a national instrument compactRIO (NI cRIO), an ABB robot, and off-the-shelf sensors. The RAMS have the ability to 3D print virtually anywhere in six degrees of freedom with very high accuracy. It is equipped with an ABB IRB 120 robot to achieve this level of accuracy. In order to convert computer-aided design (CAD) files to digital format that is acceptable to the robot, Hypertherm Robotic Software Inc.’s state-of-the-art slicing software called “ADDMAN” is used. ADDMAN is capable of converting any CAD file into RAPID code (the programing language for ABB robots). The robot uses the generated code to perform the 3D printing. To control the entire process, National Instrument (NI) compactRIO (cRio 9074), is connected and communicated with the robot and a feeding mechanism that is designed and fabricated. The feeding mechanism consists of two major parts, cold-end and hot-end. The cold-end consists of what is conventionally known as an extruder. Typically, a stepper-motor is used to control the push on the material, however, for optimum control, a DC motor is used instead. The hot-end consists of a melt-zone, nozzle, and heat-brake. The melt zone ensures a thorough melting effect and consistent output from the nozzle. Nozzles are made of brass for thermo-conductivity while the melt-zone is comprised of a heating block and a ceramic heating cartridge to transfer heat to the block. The heat-brake ensures that there is no heat creep-up effect as this would swell the material and prevent consistent extrusion. A control system embedded in the cRio is developed using NI Labview which utilizes adaptive PID to govern the heating cartridge in conjunction with a thermistor. The thermistor sends temperature feedback to the cRio, which will issue heat increase or decrease based on the system output. Since different materials have different melting points, our system will allow us to adjust the temperature and vary the material.

Keywords: robotic, additive manufacturing, PID controller, cRIO, 3D printing

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Authors: Tony Wilson

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This paper sets out a practices perspective or practices theory, which has become pervasive from business to sociological studies. In doing so, it locates the perspective historically (in the work of the philosopher Heidegger) and provides a contemporary illustration of its application to communication, consumer and cultural studies as central to this conference theme. The structured account of practices (as articulated in eight ‘axioms’) presented towards the conclusion of this paper is an initial statement - planned to encourage further detailed qualitative and systematic research in areas of interest to the conference. Practice theories of equipped and situated construction of participatory meaning (as in media and marketing consuming) are frequently characterized as lacking common ground, or core principles. This paper explores whether by retracing a journey to earlier philosophical underwriting, a shared territory promoting new research can be located as current philosophical hermeneutics. Moreover, through returning to hermeneutic first principles, the paper shows that a series of spatio-temporal metaphors become available - appropriate to analyzing communication as a process across disciplines in which it is considered. Thus one can argue, for instance, that media users engage (enter) digital text from their diverse ‘horizons of expectation’, in a productive enlarging ‘fusion’ of horizons of understanding, thereby ‘projecting’ a new narrative, integrated in a ‘hermeneutic circle’ of meaning. A politics of communication studies may contest a horizon of understanding - so engaging in critical ‘distancing’. Marketing’s consumers can occupy particular places on a horizon of understanding. Media users pass over borders of changing, revised perspectives. Practices research can now not only be discerned in multiple disciplines but equally crosses disciplines. The ubiquitous practice of media use by managers and visitors in a shopping mall - the mediatization of malls - responds to investigating not just with media study expertise, but from an interpretive marketing perspective. How have mediated identities of person or place been changed? Emphasizing understanding of entities in a material environment as ‘equipment’, practices theory enables the quantitative correlation of use and demographic variable as ‘Zeug Score’. Human behavior is fundamentally habitual - shaped by its tacit assumptions - occasionally interrupted by reflection. Practices theory acknowledges such action to be minimally monitored yet nonetheless considers it as constructing narrative. Thus presented in research, ‘storied’ behavior can then be seen to be (in)formed and shaped from a shifting hierarchy of ‘horizons’ or of perspectives - from habituated to reflective - rather than a single seamless narrative. Taking a communication practices perspective here avoids conflating tacit, transformative and theoretical understanding in research. In short, a historically grounded and unifying statement of contemporary practices theory will enhance its potential as a tool in communication, consumer and cultural research, landscaping interpretative horizons of human behaviour through exploring widely the culturally (in)formed narratives equipping and incorporated (reflectively, unreflectively) in people’s everyday lives.

Keywords: communication, consumer, cultural practices, hermeneutics

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Authors: Nabila Farhin, Israt Jahan

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Despite the feminisation of the global health force, women mostly engage in nursing, midwifery and community health workers (HWs), and the posts like surgeons, doctors, and specialists are generally male-dominated. It is also prominent in Bangladesh, where female HWs witness systematic workplace inequalities, discrimination, and underpayment. The Covid-19 pandemic put unsurmountable pressure on HWs as they had to serve in high-risk workplaces as frontliners. The already disadvantaged female HWs shouldered the same burden, were overworked without adequate occupational health and safety measures (OSH) and risked their lives. Acknowledging their vulnerable workplace conditions, the World Health Organization (WHO) and International Labour Organization (ILO) circulated a few specialised guidelines amid the peril. Bangladesh tried to adhere to international guidelines while formulating pandemic management strategies. In reality, the already weak and understaffed health sector collapsed with the patient influx and many HWs got infected and died in the line of duty, exposing the high-risk nature of the work. Unfortunately, the gender-segregated data of infected HWs are absent. This qualitative research investigates whether the existing laws of Bangladesh are adequate in protecting female HWs as frontliners in high-risk workplaces during the Covid-19 pandemic. The paper first examines international labour laws safeguarding female frontline HWs. It also analyses the specialised Covid-19 pandemic guidelines protecting their interests. Finally, the research investigates the compliance of Bangladesh as per international legal guidance during the pandemic. In doing so, it explores the domestic laws, professional guidelines for HWs and pandemic response strategies. The paper critically examines the primary sources like international and national statutes, rules, regulations and guidelines. Secondary sources like authoritative journal articles, books and newspaper reports are contextually analysed in line with the objective of the paper. The definition of HW is ambiguous in the labour laws of Bangladesh. It leads to confusion regarding the extent of legal protection rendered to female HWs at private hospitals in high-risk situations. The labour laws are not applicable in Public hospitals, as the employees follow the public service rules. Unfortunately, the country has no specialised law to protect HWs in high-risk workplaces, and the professional guidelines for HWs also remain inadequate in this regard. Even though the pandemic management strategies highlight some protective measures in high-risk situations, they only deal with HWs who are pregnant or have underlying health issues. No specialised protective guidelines can be found for female HWs as frontliners. Therefore, the laws are insufficient and failed to render adequate legal protection to female frontline HWs during the pandemic. The country also lacks comprehensive health legislation and uniform institutional and professional guidelines, preventing them from accessing grievance mechanisms. Hence, the female HWs felt victimised while duty-bound to serve in high-risk workplaces without adequate safeguards. Bangladesh should clarify the definition of HWs and standardise the service rules for providing medical care in high-risk workplaces. The research also recommends adequate health legislation and specialised legal protection to safeguard female HWs in future emergencies.

Keywords: female health workers (HWs), high-risk workplaces, Covid-19 pandemic, Bangladesh

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Authors: Sofia Dokuka, Liz Lockhart, Alex Furman

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Organizational hierarchy, traditionally composed of individual contributors, middle management, and executives, is enhanced by the understanding of informal social roles. These roles, identified with organizational network analysis (ONA), might have an important effect on organizational functioning. In this paper, we identify three social roles – influencers, bridges, and soloists, and provide empirical analysis based on real-world organizational networks. Influencers are employees with broad networks and whose contacts also have rich networks. Influence is calculated using PageRank, initially proposed for measuring website importance, but now applied in various network settings, including social networks. Influencers, having high PageRank, become key players in shaping opinions and behaviors within an organization. Bridges serve as links between loosely connected groups within the organization. Bridges are identified using betweenness and Burt’s constraint. Betweenness quantifies a node's control over information flows by evaluating its role in the control over the shortest paths within the network. Burt's constraint measures the extent of interconnection among an individual's contacts. A high constraint value suggests fewer structural holes and lesser control over information flows, whereas a low value suggests the contrary. Soloists are individuals with fewer than 5 stable social contacts, potentially facing challenges due to reduced social interaction and hypothetical lack of feedback and communication. We considered social roles in the analysis of real-world organizations (N=1,060). Based on data from digital traces (Slack, corporate email and calendar) we reconstructed an organizational communication network and identified influencers, bridges and soloists. We also collected employee engagement data through an online survey. Among the top-5% of influencers, 10% are members of the Executive Team. 56% of the Executive Team members are part of the top influencers group. The same proportion of top influencers (10%) is individual contributors, accounting for just 0.6% of all individual contributors in the company. The majority of influencers (80%) are at the middle management level. Out of all middle managers, 19% hold the role of influencers. However, individual contributors represent a small proportion of influencers, and having information about these individuals who hold influential roles can be crucial for management in identifying high-potential talents. Among the bridges, 4% are members of the Executive Team, 16% are individual contributors, and 80% are middle management. Predominantly middle management acts as a bridge. Bridge positions of some members of the executive team might indicate potential micromanagement on the leader's part. Recognizing the individuals serving as bridges in an organization uncovers potential communication problems. The majority of soloists are individual contributors (96%), and 4% of soloists are from middle management. These managers might face communication difficulties. We found an association between being an influencer and attitude toward a company's direction. There is a statistically significant 20% higher perception that the company is headed in the right direction among influencers compared to non-influencers (p < 0.05, Mann-Whitney test). Taken together, we demonstrate that considering social roles in the company might indicate both positive and negative aspects of organizational functioning that should be considered in data-driven decision-making.

Keywords: organizational network analysis, social roles, influencer, bridge, soloist

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Authors: Vaicekauskiene, G., Nabazaite, E.

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This study analyses the rise of global populism in Western democracies, focusing primarily on the populist rhetoric. Populist rhetoric is based on anti-pluralist ideas, opposing a “homogeneous nation” against “dangerous others” who are pushed out of the nation by populists, and can be citizens from both in-groups and out-groups. This study will examine the case of the elections of Parliament of the Republic of Lithuania of 2024. Fifteen candidate lists of parties and coalitions participated in the elections to the Lithuanian Parliament in 2024. Focus group methodology will be used to analyse the narratives of party supporters actively engaged in politics, trying to identify public support/opposition to populism. Liberal democracy is experiencing a crisis in both the US and Western democracies in Europe. The election results of recent years are increasingly announcing populist victories or the creation of new populist parties. Far-right parties lead the governments in three countries – Hungary, Slovakia, and Italy, and they are part of the ruling coalition in Sweden, Finland, and the Netherlands. It will become clear in the USA whether Donald Trump will be re-elected as president in November of this year. Trump’s victory in 2016 was named by political scientists as the apotheosis of populism. Influential politicians consolidate all bad manners and social categorization in the digital era of demagoguery. The research shows that a significant proportion of democratic societies also support this divisive discourse. Citizens, as consumers of information, often approve of populist communication themselves. New parliament elections were held in Lithuania in October 2024. Ideas that polarize society were amplified in the public space, negativism increased, and with it distrust towards the state, its institutions, and democratically elected politicians, “enemies” were sought and conspiracy theories were created. Problem of the Study. This study analyses the global rise of populism from the perspective of Lithuania with various groups of society, trying to understand the relationship of citizens with democracy through believing in populists, approval/disapproval of the expression of populism. Opinions are an important challenge when trying to find the truth in the age of populism, because democratic societies are based on the culture of discussion and the idea of consensus. Methodology. This study will deconstruct the narratives of Lithuanian citizens from the point of view of populism. Fifteen focus group discussions will be held with supporters of the party lists that participated in the Parliament elections of the Republic of Lithuania during November-December 2024. The main unifying criterion for focus group participants is their political activity, while the distinguishing criteria are age, gender and place of residence. Fifteen focus groups were chosen due to the fact that fifteen candidate lists of parties and coalitions participated in the elections and seeking to ensure the variety of participants. This study aims to emphasize populism as a communication phenomenon in Lithuania. Public testimonies and experiences will reveal new meanings about the understanding of populism and support/opposition towards it.

Keywords: democracy, narratives in populist rhetoric, populist rhetoric, populism

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Authors: Inna Kornienko, Svetlana Guryeva, Anatoly Shekhter, Elena Petersen

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Transplantation is an effective treatment option for patients suffering from different end-stage diseases. However, it is plagued by a constant shortage of donor organs and the subsequent need of a lifelong immunosuppressive therapy for the patient. Currently some researchers look towards using of pig organs to replace human organs for transplantation since the matrix derived from porcine organs is a convenient substitute for the human matrix. As an initial step to create a new ex vivo tissue engineered model, optimized protocols have been created to obtain organ-specific acellular matrices and evaluated their potential as tissue engineered scaffolds for culture of normal cells and tumor cell lines. These protocols include decellularization by perfusion in a bioreactor system and immersion-agitation on an orbital shaker with use of various detergents (SDS, Triton X-100) and freezing. Complete decellularization – in terms of residual DNA amount – is an important predictor of probability of immune rejection of materials of natural origin. However, the signs of cellular material may still remain within the matrix even after harsh decellularization protocols. In this regard, the matrices obtained from tissues of low-immunogenic pigs with α3Galactosyl-tranferase gene knock out (GalT-KO) may be a promising alternative to native animal sources. The research included a study of induced effect of frozen and fresh fragments of GalT-KO skin on healing of full-thickness plane wounds in 80 rats. Commercially available wound dressings (Ksenoderm, Hyamatrix and Alloderm) as well as allogenic skin were used as a positive control and untreated wounds were analyzed as a negative control. The results were evaluated on the 4th day after grafting, which corresponds to the time of start of normal wound epithelization. It has been shown that a non-specific immune response in models treated with GalT-Ko pig skin was milder than in all the control groups. Research has been performed to measure technical skin characteristics: stiffness and elasticity properties, corneometry, tevametry, and cutometry. These metrics enabled the evaluation of hydratation level, corneous layer husking level, as well as skin elasticity and micro- and macro-landscape. These preliminary data may contribute to development of personalized transplantable organs from GalT-Ko pigs with significantly limited potential of immune rejection. By applying growth factors to a decellularized skin sample it is possible to achieve various regenerative effects based on the particular situation. In this particular research BMP2 and Heparin-binding EGF-like growth factor have been used. Ideally, a bioengineered organ must be biocompatible, non-immunogenic and support cell growth. Porcine organs are attractive for xenotransplantation if severe immunologic concerns can be bypassed. The results indicate that genetically modified pig tissues with knock-outed α3Galactosyl-tranferase gene may be used for production of low-immunogenic matrix suitable for transplantation.

Keywords: decellularization, low-immunogenic, matrix, scaffolds, transplants

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Authors: Carmen Axisa, Louise Nash, Patrick Kelly, Simon Willcock

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Introduction: Doctors experience high levels of burnout, stress and psychiatric morbidity. This can affect the health of the doctor and impact patient care. Study Aims: To evaluate the effectiveness of a workshop intervention to promote wellbeing for Australian Physician Trainees. Methods: A workshop was developed in consultation with specialist clinicians to promote health and wellbeing for physician trainees. The workshop objectives were to improve participant understanding about factors affecting their health and wellbeing, to outline strategies on how to improve health and wellbeing and to encourage participants to apply these strategies in their own lives. There was a focus on building resilience and developing long term healthy behaviours as part of the physician trainee daily lifestyle. Trainees had the opportunity to learn practical strategies for stress management, gain insight into their behaviour and take steps to improve their health and wellbeing. The workshop also identified resources and support systems available to trainees. The workshop duration was four and a half hours including a thirty- minute meal break where a catered meal was provided for the trainees. Workshop evaluations were conducted at the end of the workshop. Sixty-seven physician trainees from Adult Medicine and Paediatric training programs in Sydney Australia were randomised into intervention and control groups. The intervention group attended a workshop facilitated by specialist clinicians and the control group did not. Baseline and post intervention measurements were taken for both groups to evaluate the impact and effectiveness of the workshop. Forty-six participants completed all three measurements (69%). Demographic, personal and self-reported data regarding work/life patterns was collected. Outcome measures include Depression Anxiety Stress Scale (DASS), Professional Quality of Life Scale (ProQOL) and Alcohol Use Disorders Identification Test (AUDIT). Results: The workshop was well received by the physician trainees and workshop evaluations showed that the majority of trainees strongly agree or agree that the training was relevant to their needs (96%) and met their expectations (92%). All trainees strongly agree or agree that they would recommend the workshop to their medical colleagues. In comparison to the control group we observed a reduction in alcohol use, depression and burnout but an increase in stress, anxiety and secondary traumatic stress in the intervention group, at the primary endpoint measured at 6 months. However, none of these differences reached statistical significance (p > 0.05). Discussion: Although the study did not reach statistical significance, the workshop may be beneficial to physician trainees. Trainees had the opportunity to share ideas, gain insight into their own behaviour, learn practical strategies for stress management and discuss approach to work, life and self-care. The workshop discussions enabled trainees to share their experiences in a supported environment where they learned that other trainees experienced stress and burnout and they were not alone in needing to acquire successful coping mechanisms and stress management strategies. Conclusion: These findings suggest that physician trainees are a vulnerable group who may benefit from initiatives that promote wellbeing and from a more supportive work environment.

Keywords: doctors' health, physician burnout, physician resilience, wellbeing workshop

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Authors: Leander Van Neste, Kirk Wojno

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The innate immune system reacts to foreign insult in several unique ways, one of which is phagocytosis of perceived threats such as cancer, bacteria, and viruses. The goal of this study was to look for evidence of phagocytosed RNA from tumor cells in circulating monocytes. While all monocytes possess phagocytic capabilities, the non-classical CD14+/FCGR3A+ monocytes and the intermediate CD14++/FCGR3A+ monocytes most actively remove threatening ‘external’ cellular materials. Purified CD14-positive monocyte samples from fourteen patients recently diagnosed with clinically localized prostate cancer (PCa) were investigated by single-cell RNA sequencing using the 10X Genomics protocol followed by paired-end sequencing on Illumina’s NovaSeq. Similarly, samples were processed and used as controls, i.e., one patient underwent biopsy but was found not to harbor prostate cancer (benign), three young, healthy men, and three men previously diagnosed with prostate cancer that recently underwent (curative) radical prostatectomy (post-RP). Sequencing data were mapped using 10X Genomics’ CellRanger software and viable cells were subsequently identified using CellBender, removing technical artifacts such as doublets and non-cellular RNA. Next, data analysis was performed in R, using the Seurat package. Because the main goal was to identify differences between PCa patients and ‘control’ patients, rather than exploring differences between individual subjects, the individual Seurat objects of all 21 patients were merged into one Seurat object per Seurat’s recommendation. Finally, the single-cell dataset was normalized as a whole prior to further analysis. Cell identity was assessed using the SingleR and cell dex packages. The Monaco Immune Data was selected as the reference dataset, consisting of bulk RNA-seq data of sorted human immune cells. The Monaco classification was supplemented with normalized PCa data obtained from The Cancer Genome Atlas (TCGA), which consists of bulk RNA sequencing data from 499 prostate tumor tissues (including 1 metastatic) and 52 (adjacent) normal prostate tissues. SingleR was subsequently run on the combined immune cell and PCa datasets. As expected, the vast majority of cells were labeled as having a monocytic origin (~90%), with the most noticeable difference being the larger number of intermediate monocytes in the PCa patients (13.6% versus 7.1%; p<.001). In men harboring PCa, 0.60% of all purified monocytes were classified as harboring PCa signals when the TCGA data were included. This was 3-fold, 7.5-fold, and 4-fold higher compared to post-RP, benign, and young men, respectively (all p<.001). In addition, with 7.91%, the number of unclassified cells, i.e., cells with pruned labels due to high uncertainty of the assigned label, was also highest in men with PCa, compared to 3.51%, 2.67%, and 5.51% of cells in post-RP, benign, and young men, respectively (all p<.001). It can be postulated that actively phagocytosing cells are hardest to classify due to their dual immune cell and foreign cell nature. Hence, the higher number of unclassified cells and intermediate monocytes in PCa patients might reflect higher phagocytic activity due to tumor burden. This also illustrates that small numbers (~1%) of circulating peripheral blood monocytes that have interacted with tumor cells might still possess detectable phagocytosed tumor RNA.

Keywords: circulating monocytes, phagocytic cells, prostate cancer, tumor immune response

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Authors: Bahareh Ansari

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Background: The Open Government Data (OGD) movement in the last decade has encouraged many government organizations around the world to make their data publicly available to advance democratic processes. But current open data platforms have not yet reached to their full potential in supporting all interested parties. To make the data useful and understandable for everyone, scholars suggested that opening the data should be supplemented by visualization. However, different visualizations of the same information can dramatically change an individual’s cognitive and emotional experience in working with the data. This study reviews the data visualization literature to create a list of the methods empirically tested to enhance users’ performance and experience in working with a visualization tool. This list can be used in evaluating the OGD visualization practices and informing the future open data initiatives. Methods: Previous reviews of visualization literature categorized the visualization outcomes into four categories including recall/memorability, insight/comprehension, engagement, and enjoyment. To identify the papers, a search for these outcomes was conducted in the abstract of the publications of top-tier visualization venues including IEEE Transactions for Visualization and Computer Graphics, Computer Graphics, and proceedings of the CHI Conference on Human Factors in Computing Systems. The search results are complemented with a search in the references of the identified articles, and a search for 'open data visualization,' and 'visualization evaluation' keywords in the IEEE explore and ACM digital libraries. Articles are included if they provide empirical evidence through conducting controlled user experiments, or provide a review of these empirical studies. The qualitative synthesis of the studies focuses on identification and classifying the methods, and the conditions under which they are examined to positively affect the visualization outcomes. Findings: The keyword search yields 760 studies, of which 30 are included after the title/abstract review. The classification of the included articles shows five distinct methods: interactive design, aesthetic (artistic) style, storytelling, decorative elements that do not provide extra information including text, image, and embellishment on the graphs), and animation. Studies on decorative elements show consistency on the positive effects of these elements on user engagement and recall but are less consistent in their examination of the user performance. This inconsistency could be attributable to the particular data type or specific design method used in each study. The interactive design studies are consistent in their findings of the positive effect on the outcomes. Storytelling studies show some inconsistencies regarding the design effect on user engagement, enjoyment, recall, and performance, which could be indicative of the specific conditions required for the use of this method. Last two methods, aesthetics and animation, have been less frequent in the included articles, and provide consistent positive results on some of the outcomes. Implications for e-government: Review of the visualization best-practice methods show that each of these methods is beneficial under specific conditions. By using these methods in a potentially beneficial condition, OGD practices can promote a wide range of individuals to involve and work with the government data and ultimately engage in government policy-making procedures.

Keywords: best practices, data visualization, literature review, open government data

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Authors: Babak Forouraghi

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A genetic circuit is a collection of interacting genes and proteins that enable individual cells to implement and perform vital biological functions such as cell division, growth, death, and signaling. In cell engineering, synthetic gene circuits are engineered networks of genes specifically designed to implement functionalities that are not evolved by nature. These engineered networks enable scientists to tackle complex problems such as engineering cells to produce therapeutics within the patient's body, altering T cells to target cancer-related antigens for treatment, improving antibody production using engineered cells, tissue engineering, and production of genetically modified plants and livestock. Construction of computational models to realize genetic circuits is an especially challenging task since it requires the discovery of flow of genetic information in complex biological systems. Building synthetic biological models is also a time-consuming process with relatively low prediction accuracy for highly complex genetic circuits. The primary goal of this study was to investigate the utility of a pre-trained bidirectional encoder transformer that can accurately predict gene expressions in genetic circuit designs. The main reason behind using transformers is their innate ability (attention mechanism) to take account of the semantic context present in long DNA chains that are heavily dependent on spatial representation of their constituent genes. Previous approaches to gene circuit design, such as CNN and RNN architectures, are unable to capture semantic dependencies in long contexts as required in most real-world applications of synthetic biology. For instance, RNN models (LSTM, GRU), although able to learn long-term dependencies, greatly suffer from vanishing gradient and low-efficiency problem when they sequentially process past states and compresses contextual information into a bottleneck with long input sequences. In other words, these architectures are not equipped with the necessary attention mechanisms to follow a long chain of genes with thousands of tokens. To address the above-mentioned limitations of previous approaches, a transformer model was built in this work as a variation to the existing DNA Bidirectional Encoder Representations from Transformers (DNABERT) model. It is shown that the proposed transformer is capable of capturing contextual information from long input sequences with attention mechanism. In a previous work on genetic circuit design, the traditional approaches to classification and regression, such as Random Forrest, Support Vector Machine, and Artificial Neural Networks, were able to achieve reasonably high R2 accuracy levels of 0.95 to 0.97. However, the transformer model utilized in this work with its attention-based mechanism, was able to achieve a perfect accuracy level of 100%. Further, it is demonstrated that the efficiency of the transformer-based gene expression classifier is not dependent on presence of large amounts of training examples, which may be difficult to compile in many real-world gene circuit designs.

Keywords: transformers, generative ai, gene expression design, classification

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Authors: Jacqueline Eleonora Ek, Michael Spiteri, Chris Giordimaina, Pierre Agius

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Background: Malta is known for being a key player as a frontline country with regard to irregular immigration from Africa to Europe. Every year the island experiences an influx of migrants as boat movement across the Mediterranean continues to be a humanitarian challenge. Irregular immigration and applying for asylum is both a lengthy and mentally demanding process. Those doing so are often faced with multiple challenges, which can adversely affect their mental health. Between January and August 2020, Malta disembarked 2 162 people rescued at sea, 463 of them between July & August. Given the small size of the Maltese islands, this regulation places a disproportionately large burden on the country, creating a backlog in the processing of asylum applications resulting in increased time periods of detention. These delays reverberate throughout multiple management pathways resulting in prolonged periods of detention and challenging access to health services. Objectives: To better understand the spatial dimensions of this humanitarian crisis, this study aims to assess disparities in the acute medical management of migrants presenting to the emergency department (ED) with acute mental health presentations as compared to that of local and non-local residents. Method: In this retrospective study, 17795 consecutive ED attendances were reviewed to look for acute mental health presentations. These were further evaluated to assess discrepancies in transportation routes to hospital, nature of presenting complaint, effects of language barriers, use of CT brain, treatment given at ED, availability of psychiatric reviews, and final admission/discharge plans. Results: Of the ED attendances, 92.3% were local residents, and 7.7% were non-locals. Of the non-locals, 13.8% were migrants, and 86.2% were other-non-locals. Acute mental health presentations were seen in 1% of local residents; this increased to 20.6% in migrants. 56.4% of migrants attended with deliberate self-harm; this was lower in local residents, 28.9%. Contrastingly, in local residents, the most common presenting complaint was suicidal thought/ low mood 37.3%, the incidence was similar in migrants at 33.3%. The main differences included 12.8% of migrants presenting with refused oral intake while only 0.6% of local residents presented with the same complaints. 7.7% of migrants presented with a reduced level of consciousness, no local residents presented with this same issue. Physicians documented a language barrier in 74.4% of migrants. 25.6% were noted to be completely uncommunicative. Further investigations included the use of a CT scan in 12% of local residents and in 35.9% of migrants. The most common treatment administered to migrants was supportive fluids 15.4%, the most common in local residents was benzodiazepines 15.1%. Voluntary psychiatric admissions were seen in 33.3% of migrants and 24.7% of locals. Involuntary admissions were seen in 23% of migrants and 13.3% of locals. Conclusion: Results showed multiple disparities in health management. A meeting was held between entities responsible for migrant health in Malta, including the emergency department, primary health care, migrant detention services, and Malta Red Cross. Currently, national quality-improvement initiatives are underway to form new pathways to improve patient-centered care. These include an interpreter unit, centralized handover sheets, and a dedicated migrant health service.

Keywords: emergency department, communication, health, migration

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Authors: Sree Bash Chandra Debnath, Didier Tonneau, Carole Fauquet, Agnes Tallet, Julien Darreon

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Purpose: Inorganic scintillating dosimetry is the most recent promising technique to solve several dosimetric issues and provide quality assurance in radiation therapy. Despite several advantages, the major issue of using scintillating detectors is the Cerenkov effect, typically induced in the visible emission range. In this context, the purpose of this research work is to evaluate the performance of a novel infrared inorganic scintillator detector (IR-ISD) in the radiation therapy treatment to ensure Cerenkov free signal and the best matches between the delivered and prescribed doses during treatment. Methods: A simple and small-scale infrared inorganic scintillating detector of 100 µm diameter with a sensitive scintillating volume of 2x10-6 mm3 was developed. A prototype of the dose verification system has been introduced based on PTIR1470/F (provided by Phosphor Technology®) material used in the proposed novel IR-ISD. The detector was tested on an Elekta LINAC system tuned at 6 MV/15MV and a brachytherapy source (Ir-192) used in the patient treatment protocol. The associated dose rate was measured in count rate (photons/s) using a highly sensitive photon counter (sensitivity ~20ph/s). Overall measurements were performed in IBATM water tank phantoms by following international Technical Reports series recommendations (TRS 381) for radiotherapy and TG43U1 recommendations for brachytherapy. The performance of the detector was tested through several dosimetric parameters such as PDD, beam profiling, Cerenkov measurement, dose linearity, dose rate linearity repeatability, and scintillator stability. Finally, a comparative study is also shown using a reference microdiamond dosimeter, Monte-Carlo (MC) simulation, and data from recent literature. Results: This study is highlighting the complete removal of the Cerenkov effect especially for small field radiation beam characterization. The detector provides an entire linear response with the dose in the 4cGy to 800 cGy range, independently of the field size selected from 5 x 5 cm² down to 0.5 x 0.5 cm². A perfect repeatability (0.2 % variation from average) with day-to-day reproducibility (0.3% variation) was observed. Measurements demonstrated that ISD has superlinear behavior with dose rate (R2=1) varying from 50 cGy/s to 1000 cGy/s. PDD profiles obtained in water present identical behavior with a build-up maximum depth dose at 15 mm for different small fields irradiation. A low dimension of 0.5 x 0.5 cm² field profiles have been characterized, and the field cross profile presents a Gaussian-like shape. The standard deviation (1σ) of the scintillating signal remains within 0.02% while having a very low convolution effect, thanks to lower sensitive volume. Finally, during brachytherapy, a comparison with MC simulations shows that considering energy dependency, measurement agrees within 0.8% till 0.2 cm source to detector distance. Conclusion: The proposed scintillating detector in this study shows no- Cerenkov radiation and efficient performance for several radiation therapy measurement parameters. Therefore, it is anticipated that the IR-ISD system can be promoted to validate with direct clinical investigations, such as appropriate dose verification and quality control in the Treatment Planning System (TPS).

Keywords: IR-Scintillating detector, dose measurement, micro-scintillators, Cerenkov effect

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Authors: V. V. Fomin, A. P. Mikhailovich, E. M. Agapitov, V. E. Rogachev, E. A. Kostousova, E. S. Perekhodova

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Ground-level landscape photos can be used as a source of objective data on woody vegetation and vegetation dynamics. We proposed a method for processing, analyzing, and presenting ground photographs, which has the following advantages: 1) researcher has to form holistic representation of the study area in form of a set of interlapping ground-level landscape photographs; 2) it is necessary to define or obtain characteristics of the landscape, objects, and phenomena present on the photographs; 3) it is necessary to create new or supplement existing textual descriptions and annotations for the ground-level landscape photographs; 4) single or multiple ground-level landscape photographs can be used to develop specialized geoinformation layers, schematic maps or thematic maps; 5) it is necessary to determine quantitative data that describes both images as a whole, and displayed objects and phenomena, using algorithms for automated image analysis. It is suggested to match each photo with a polygonal geoinformation layer, which is a sector consisting of areas corresponding with parts of the landscape visible in the photos. Calculation of visibility areas is performed in a geoinformation system within a sector using a digital model of a study area relief and visibility analysis functions. Superposition of the visibility sectors corresponding with various camera viewpoints allows matching landscape photos with each other to create a complete and wholesome representation of the space in question. It is suggested to user-defined data or phenomenons on the images with the following superposition over the visibility sector in the form of map symbols. The technology of geoinformation layers’ spatial superposition over the visibility sector creates opportunities for image geotagging using quantitative data obtained from raster or vector layers within the sector with the ability to generate annotations in natural language. The proposed method has proven itself well for relatively open and clearly visible areas with well-defined relief, for example, in mountainous areas in the treeline ecotone. When the polygonal layers of visibility sectors for a large number of different points of photography are topologically superimposed, a layer of visibility of sections of the entire study area is formed, which is displayed in the photographs. Also, as a result of this overlapping of sectors, areas that did not appear in the photo will be assessed as gaps. According to the results of this procedure, it becomes possible to obtain information about the photos that display a specific area and from which points of photography it is visible. This information may be obtained either as a query on the map or as a query for the attribute table of the layer. The method was tested using repeated photos taken from forty camera viewpoints located on Ray-Iz mountain massif (Polar Urals, Russia) from 1960 until 2023. It has been successfully used in combination with other ground-based and remote sensing methods of studying the climate-driven dynamics of woody vegetation in the Polar Urals. Acknowledgment: This research was collaboratively funded by the Russian Ministry for Science and Education project No. FEUG-2023-0002 (image representation) and Russian Science Foundation project No. 24-24-00235 (automated textual description).

Keywords: woody, vegetation, repeated, photographs

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Authors: Hiroshi Kinoshita, Yasuto Nakanishi, Ryuhei Okuno, Toshio Higashi

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Various kinds of pegboards have been developed and used widely in research and clinics of rehabilitation for evaluation and training of patient’s hand function. A common measure in these peg boards is a total time of performance execution assessed by a tester’s stopwatch. Introduction of electrical and automatic measurement technology to the apparatus, on the other hand, has been delayed. The present work introduces the development of a pegboard with an electric sensor to detect moments of individual peg’s insertion and removal. The work also gives fundamental data obtained from a group of healthy young individuals who performed peg transfer tasks using the pegboard developed. Through trails and errors in pilot tests, two 10-hole peg-board boxes installed with a small photo-reflector and a DC amplifier at the bottom of each hole were designed and built by the present authors. The amplified electric analogue signals from the 20 reflectors were automatically digitized at 500 Hz per channel, and stored in a PC. The boxes were set on a test table at different distances (25, 50, 75, and 125 mm) in parallel to examine the effect of hole-to-hole distance. Fifty healthy young volunteers (25 in each gender) as subjects of the study performed successive fast 80 time peg transfers at each distance using their dominant and non-dominant hands. The data gathered showed a clear-cut light interruption/continuation moment by the pegs, allowing accurately (no tester’s error involved) and precisely (an order of milliseconds) to determine the pull out and insertion times of each peg. This further permitted computation of individual peg movement duration (PMD: from peg-lift-off to insertion) apart from hand reaching duration (HRD: from peg insertion to lift-off). An accidental drop of a peg led to an exceptionally long ( < mean + 3 SD) PMD, which was readily detected from an examination of data distribution. The PMD data were commonly right-skewed, suggesting that the median can be a better estimate of individual PMD than the mean. Repeated measures ANOVA using the median values revealed significant hole-to-hole distance, and hand dominance effects, suggesting that these need to be fixed in the accurate evaluation of PMD. The gender effect was non-significant. Performance consistency was also evaluated by the use of quartile variation coefficient values, which revealed no gender, hole-to-hole, and hand dominance effects. The measurement reliability was further examined using interclass correlation obtained from 14 subjects who performed the 25 and 125 mm hole distance tasks at two 7-10 days separate test sessions. Inter-class correlation values between the two tests showed fair reliability for PMD (0.65-0.75), and for HRD (0.77-0.94). We concluded that a sensor peg board developed in the present study could provide accurate (excluding tester’s errors), and precise (at a millisecond rate) time information of peg movement separated from that used for hand movement. It could also easily detect and automatically exclude erroneous execution data from his/her standard data. These would lead to a better evaluation of hand dexterity function compared to the widely used conventional used peg boards.

Keywords: hand, dexterity test, peg movement time, performance consistency

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Authors: Noury Bakrim

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When dealing with motivation/arbitrariness, forming form (Forma Formans) and morphodynamics are to be grasped as relevant implications of enunciation/enactment, schematization within the specificity of language as sound/meaning articulation. Thus, the fact that a language is a form does not contradict stasis/dynamic enunciation (reflexivity vs double articulation). Moreover, some languages exemplify the role of the forming form, uttering, and schematization (roots in Semitic languages, the Chinese case). Beyond the evolutionary biosemiotic process (form/substance bifurcation, the split between realization/representation), non-isomorphism/asymmetry between linguistic form/norm and linguistic realization (phonetics for instance) opens up a new horizon problematizing the role of Brain – sensorimotor contribution in the continuous forming form. Therefore, we hypothesize biotization as both process/trace co-constructing motivation/forming form. Henceforth, referring to our findings concerning distribution and motivation patterns within Berber written texts (pulse based obstruents and nasal-lateral levels in poetry) and oral storytelling (consonant intensity clustering in quantitative and semantic/prosodic motivation), we understand consonant clustering, motivation and schematization as a complex phenomenon partaking in patterns of oral/written iconic prosody and reflexive metalinguistic representation opening the stable form. We focus our inquiry on both Amazigh and English clusters (/spl/, /spr/) and iconic consonant iteration in [gnunnuy] (to roll/tumble), [smummuy] (to moan sadly or crankily). For instance, the syllabic structures of /splaeʃ/ and /splaet/ imply an anamorphic representation of the state of the world: splash, impact on aquatic surfaces/splat impact on the ground. The pair has stridency and distribution as distinctive features which specify its phonetic realization (and a part of its meaning) /ʃ/ is [+ strident] and /t/ is [+ distributed] on the vocal tract. Schematization is then a process relating both physiology/code as an arthron vocal/bodily, vocal/practical shaping of the motor-articulatory system, leading to syntactic/semantic thematization (agent/patient roles in /spl/, /sm/ and other clusters or the tense uvular /qq/ at the initial position in Berber). Furthermore, the productivity of serial syllable sequencing in Berber points out different expressivity forms. We postulate two Components of motivated formalization: i) the process of memory paradigmatization relating to sequence modeling under sensorimotor/verbal specific categories (production/perception), ii) the process of phonotactic selection - prosodic unconscious/subconscious distribution by virtue of iconicity. Basing on multiple tests including a questionnaire, phonotactic/visual recognition and oral/written reproduction, we aim at patterning/conceptualizing consonant schematization and motivation among EFL and Amazigh (Berber) learners and speakers integrating biolinguistic hypotheses.

Keywords: consonant motivation and prosody, language and order of life, anamorphic representation, represented representation, biotization, sensori-motor and brain representation, form, formalization and schematization

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Authors: Jiri Nepereny, Vladimir Vrzal

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Staphylococcus intermedius/pseudintermedius bacteria are commonly found on the skin of healthy dogs and can cause pruritic skin diseases under certain circumstances (trauma, allergy, immunodeficiency, ectoparasitosis, endocrinological diseases, glucocorticoid therapy, etc.). These can develop into complicated superficial or deep pyoderma, which represent a large group of problematic skin diseases in dogs. These are predominantly inflammations of a secondary nature, associated with the occurrence of coagulase-positive Staphylococcus spp. A major problem is increased itching, which greatly complicates the healing process. The aim of this work is to verify the efficacy of the developed preparation Bacteriophage SI (Staphylococcus intermedius). The tested preparation contains a lysate of bacterial cells of S. intermedius host culture including culture medium and live virions of specific phage. Sodium Merthiolate is added as a preservative in a safe concentration. Validation of the efficacy of the product was demonstrated by monitoring the therapeutic effect after application to indicated cases from clinical practice. The indication for inclusion of the patient into the trial was an adequate history and clinical examination accompanied by sample collection for bacteriological examination and isolation of the specific causative agent. Isolate identification was performed by API BioMérieux identification system (API ID 32 STAPH) and rep-PCR typing. The suitability of therapy for a specific case was confirmed by in vitro testing of the lytic ability of the bacteriophage to lyse the specific isolate = formation of specific plaques on the culture isolate on the surface of the solid culture medium. So far, a total of 32 dogs of different sexes, ages and breed affiliations with different symptoms of staphylococcal dermatitis have been included in the testing. Their previous therapy consisted of more or less successful systemic or local application of broad-spectrum antibiotics. The presence of S. intermedius/pseudintermedius has been demonstrated in 26 cases. The isolates were identified as a S. pseudintermedius, in all cases. Contaminant bacterial microflora was always present in the examined samples. The test product was applied subcutaneously in gradually increasing doses over a period of 1 month. After improvement in health status, maintenance therapy was followed by application of the product once a week for 3 months. Adverse effects associated with the administration of the product (swelling at the site of application) occurred in only 2 cases. In all cases, there was a significant reduction in clinical signs (healing of skin lesions and reduction of inflammation) after therapy and an improvement in the well-being of the treated animals. A major problem in the treatment of pyoderma is the frequent resistance of the causative agents to antibiotics, especially the increasing frequency of multidrug-resistant and methicillin-resistant S. pseudintermedius (MRSP) strains. Specific phagolysate using for the therapy of these diseases could solve this problem and to some extent replace or reduce the use of antibiotics, whose frequent and widespread application often leads to the emergence of resistance. The advantage of the therapeutic use of bacteriophages is their bactericidal effect, high specificity and safety. This work was supported by Project FV40213 from Ministry of Industry and Trade, Czech Republic.

Keywords: bacteriophage, pyoderma, staphylococcus spp, therapy

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Authors: Omer Zvi Shaked, Amir Tirosh

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Type 1 Diabetes (T1DM) is an incurable chronic illness with no known preventive measures. Excess to insulin therapy can lead to hypoglycemia with neuro-glycogenic symptoms such as shakiness, nausea, sweating, irritability, fatigue, excessive thirst or hunger, weakness, seizure, and coma. Severe Hypoglycemia (SH) is also considered a most aversive event since it may put patients at risk for injury and death, which matches the criteria of a traumatic event. SH has a ranging prevalence of 20%, which makes it a primary medical Issue. One of the results of SH is an intense emotional fear reaction resembling the form of post-traumatic stress symptoms (PTS), causing many patients to avoid insulin therapy and social activities in order to avoid the possibility of hypoglycemia. As a result, they are at risk for irreversible health deterioration and medical complications. Fear of Hypoglycemia (FOH) is, therefore, a major disturbance for T1DM patients. FOH differs from prevalent post-traumatic stress reactions to other forms of traumatic events since the threat to life continuously exists in the patient's body. That is, it is highly probable that orthodox interventions may not be sufficient for helping patients after SH to regain healthy social function and proper medical treatment. Accordingly, the current presentation will demonstrate the results of a study conducted among T1DM patients after SH. The study was designed in two stages. First, a preliminary qualitative phenomenological study among ten patients after SH was conducted. Analysis revealed that after SH, patients confuse between stress symptoms and Hypoglycemia symptoms, divide life before and after the event, report a constant sense of fear, a loss of freedom, a significant decrease in social functioning, a catastrophic thinking pattern, a dichotomous split between the self and the body, and internalization of illness identity, a loss of internal locus of control, a damaged self-representation, and severe loneliness for never being understood by others. The second stage was a two steps study of intervention among five patients after SH. The first part of the intervention included three months of therapeutic 3rd wave CBT therapy. The contents of the therapeutic process were: acceptance of fear and tolerance to stress; cognitive de-fusion combined with emotional self-regulation; the adoption of an active position relying on personal values; and self-compassion. Then, the intervention included a one-week practical real-time 24/7 support by trained medical personnel, alongside a gradual exposure to increased insulin therapy in a protected environment. The results of the intervention are a decrease in stress symptoms, increased social functioning, increased well-being, and decreased avoidance of medical treatment. The presentation will discuss the unique emotional state of T1DM patients after SH. Then, the presentation will discuss the effectiveness of the intervention for patients with chronic conditions after a traumatic event. The presentation will make evident the unique situation of illness-related PTSD. The presentation will also demonstrate the requirement for multi-professional collaboration between social work and medical care for populations with chronic medical conditions. Limitations of the study and recommendations for further research will be discussed.

Keywords: type 1 diabetes, chronic illness, post-traumatic stress, illness-related PTSD

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Authors: Maddalena Arigoni, Maria Luisa Ratto, Raffaele A. Calogero, Luca Alessandri

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The presence of tumor heterogeneity, where distinct cancer cells exhibit diverse morphological and phenotypic profiles, including gene expression, metabolism, and proliferation, poses challenges for molecular prognostic markers and patient classification for targeted therapies. Understanding the causes and progression of cancer requires research efforts aimed at characterizing heterogeneity, which can be facilitated by evolving single-cell sequencing technologies. However, analyzing single-cell data necessitates computational methods that often lack objective validation. Therefore, the establishment of benchmarking datasets is necessary to provide a controlled environment for validating bioinformatics tools in the field of single-cell oncology. Benchmarking bioinformatics tools for single-cell experiments can be costly due to the high expense involved. Therefore, datasets used for benchmarking are typically sourced from publicly available experiments, which often lack a comprehensive cell annotation. This limitation can affect the accuracy and effectiveness of such experiments as benchmarking tools. To address this issue, we introduce omics benchmark experiments designed to evaluate bioinformatics tools to depict the heterogeneity in single-cell tumor experiments. We conducted single-cell RNA sequencing on six lung cancer tumor cell lines that display resistant clones upon treatment of EGFR mutated tumors and are characterized by driver genes, namely ROS1, ALK, HER2, MET, KRAS, and BRAF. These driver genes are associated with downstream networks controlled by EGFR mutations, such as JAK-STAT, PI3K-AKT-mTOR, and MEK-ERK. The experiment also featured an EGFR-mutated cell line. Using 10XGenomics platform with cellplex technology, we analyzed the seven cell lines together with a pseudo-immunological microenvironment consisting of PBMC cells labeled with the Biolegend TotalSeq™-B Human Universal Cocktail (CITEseq). This technology allowed for independent labeling of each cell line and single-cell analysis of the pooled seven cell lines and the pseudo-microenvironment. The data generated from the aforementioned experiments are available as part of an online tool, which allows users to define cell heterogeneity and generates count tables as an output. The tool provides the cell line derivation for each cell and cell annotations for the pseudo-microenvironment based on CITEseq data by an experienced immunologist. Additionally, we created a range of pseudo-tumor tissues using different ratios of the aforementioned cells embedded in matrigel. These tissues were analyzed using 10XGenomics (FFPE samples) and Curio Bioscience (fresh frozen samples) platforms for spatial transcriptomics, further expanding the scope of our benchmark experiments. The benchmark experiments we conducted provide a unique opportunity to evaluate the performance of bioinformatics tools for detecting and characterizing tumor heterogeneity at the single-cell level. Overall, our experiments provide a controlled and standardized environment for assessing the accuracy and robustness of bioinformatics tools for studying tumor heterogeneity at the single-cell level, which can ultimately lead to more precise and effective cancer diagnosis and treatment.

Keywords: single cell omics, benchmark, spatial transcriptomics, CITEseq

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Authors: Piotr Wadolowski, Grzegorz Krzesinski, Piotr Gutowski

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The aim of the presented investigation is to recognize the possible mechanical issues of mini-plate connection used to treat mandible fractures and to check the impact of different factors for the stresses and displacements within the bone-stabilizer system. The mini-plate osteosynthesis technique is a common type of internal fixation using metal plates connected to the fractured bone parts by a set of screws. The selected two types of plate application methodology used by maxillofacial surgeons were investigated in the work. Those patterns differ in location and number of plates. The bone geometry was modeled on the base of computed tomography scans of hospitalized patient done just after mini-plate application. The solid volume geometry consisting of cortical and cancellous bone was created based on gained cloud of points. Temporomandibular joint and muscle system were simulated to imitate the real masticatory system behavior. Finite elements mesh and analysis were performed by ANSYS software. To simulate realistic connection behavior nonlinear contact conditions were used between the connecting elements and bones. The influence of the initial compression of the connected bone parts or the gap between them was analyzed. Nonlinear material properties of the bone tissues and elastic-plastic model of titanium alloy were used. The three cases of loading assuming the force of magnitude of 100N acting on the left molars, the right molars and the incisors were investigated. Stress distribution within connecting plate shows that the compression of the bone parts in the connection results in high stress concentration in the plate and the screws, however the maximum stress levels do not exceed material (titanium) yield limit. There are no significant differences between negative offset (gap) and no-offset conditions. The location of the external force influences the magnitude of stresses around both the plate and bone parts. Two-plate system gives generally lower von Misses stress under the same loading than the one-plating approach. Von Mises stress distribution within the cortical bone shows reduction of high stress field for the cases without the compression (neutral initial contact). For the initial prestressing there is a visible significant stress increase around the fixing holes at the bottom mini-plate due to the assembly stress. The local stress concentration may be the reason of bone destruction in those regions. The performed calculations prove that the bone-mini-plate system is able to properly stabilize the fractured mandible bone. There is visible strong dependency between the mini-plate location and stress distribution within the stabilizer structure and the surrounding bone tissue. The results (stresses within the bone tissues and within the devices, relative displacements of the bone parts at the interface) corresponding to different models of the connection provide a basis for the mechanical optimization of the mini-plate connections. The results of the performed numerical simulations were compared to clinical observation. They provide information helpful for better understanding of the load transfer in the mandible with the stabilizer and for improving stabilization techniques.

Keywords: finite element modeling, mandible fracture, mini-plate connection, osteosynthesis

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