Search results for: end stage renal disease

Authors: Anupama Singh, Papia Raj

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Though Municipal Solid Waste (MSW) is a worldwide problem, yet its implications are enormous in developing countries, as they are unable to provide proper Municipal Solid Waste Management (MSWM) for the large volume of MSW. As a result, the collected wastes are dumped in open dumping at landfilling sites while the uncollected wastes remain strewn on the roadside, many-a-time clogging drainage. Such unsafe and inadequate management of MSW causes various public health hazards. For example, MSW directly on contact or by leachate contaminate the soil, surface water, and ground water; open burning causes air pollution; anaerobic digestion between the piles of MSW enhance the greenhouse gases i.e., carbon dioxide and methane (CO2 and CH4) into the atmosphere. Moreover, open dumping can cause spread of vector borne disease like cholera, typhoid, dysentery, and so on. Patna, the capital city of Bihar, one of the most underdeveloped provinces in India, is a unique representation of this situation. Patna has been identified as the ‘garbage city’. Over the last decade there has been an exponential increase in the quantity of MSW generation in Patna. Though a large proportion of such MSW is recyclable in nature, only a negligible portion is recycled. Plastic constitutes the major chunk of the recyclable waste. The chemical composition of plastic is versatile consisting of toxic compounds, such as, plasticizers, like adipates and phthalates. Pigmented plastic is highly toxic and it contains harmful metals such as copper, lead, chromium, cobalt, selenium, and cadmium. Human population becomes vulnerable to an array of health problems as they are exposed to these toxic chemicals multiple times a day through air, water, dust, and food. Based on analysis of health data it can be emphasized that in Patna there has been an increase in the incidence of specific diseases, such as, diarrhoea, dysentry, acute respiratory infection (ARI), asthma, and other chronic respiratory diseases (CRD). This trend can be attributed to improper MSWM. The results were reiterated through a survey (N=127) conducted during 2014-15 in selected areas of Patna. Random sampling method of data collection was used to better understand the relationship between different variables affecting public health due to exposure to MSW and lack of MSWM. The results derived through bivariate and logistic regression analysis of the survey data indicate that segregation of wastes at source, segregation behavior, collection bins in the area, distance of collection bins from residential area, and transportation of MSW are the major determinants of public health issues. Sustainable recycling is a robust method for MSWM with its pioneer concerns being environment, society, and economy. It thus ensures minimal threat to environment and ecology consequently improving public health conditions. Hence, this paper concludes that sustainable recycling would be the most viable approach to manage MSW in Patna and would eventually reduce public health hazards.

Keywords: municipal solid waste, Patna, public health, sustainable recycling

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Authors: Omer Leshem, Michael F. Schober

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This paper introduces a new method for assessing how audience members and performers feel and think during live concerts, and how audience members' recognized and felt emotions are related. Two hypotheses were tested in a live concert setting: (1) that audience members’ cognitive perspective taking ability predicts their accuracy in identifying an emotion that a jazz improviser intended to express during a performance, and (2) that audience members' affective empathy predicts their likelihood of feeling the same emotions as the performer. The aim was to stage a concert with audience members who regularly attend live jazz performances, and to measure their cognitive and affective reactions during the performance as non-intrusively as possible. Pianist and Grammy nominee Andy Milne agreed, without knowing details of the method or hypotheses, to perform a full-length solo improvised concert that would include an ‘unusual’ piece. Jazz fans were recruited through typical advertising for New York City jazz performances. The event was held at the New School’s Glass Box Theater, the home of leading NYC jazz venue ‘The Stone.’ Audience members were charged typical NYC jazz club admission prices; advertisements informed them that anyone who chose to participate in the study would be reimbursed their ticket price after the concert. The concert, held in April 2018, had 30 attendees, 23 of whom participated in the study. Twenty-two minutes into the concert, the performer was handed a paper note with the instruction: ‘Perform a 3-5-minute improvised piece with the intention of conveying sadness.’ (Sadness was chosen based on previous music cognition lab studies, where solo listeners were less likely to select sadness as the musically-expressed emotion accurately from a list of basic emotions, and more likely to misinterpret sadness as tenderness). Then, audience members and the performer were invited to respond to a questionnaire from a first envelope under their seat. Participants used their own words to describe the emotion the performer had intended to express, and then to select the intended emotion from a list. They also reported the emotions they had felt while listening using Izard’s differential emotions scale. The concert then continued as usual. At the end, participants answered demographic questions and Davis’ interpersonal reactivity index (IRI), a 28-item scale designed to assess both cognitive and affective empathy. Hypothesis 1 was supported: audience members with greater cognitive empathy were more likely to accurately identify sadness as the expressed emotion. Moreover, audience members who accurately selected ‘sadness’ reported feeling marginally sadder than people who did not select sadness. Hypotheses 2 was not supported; audience members with greater affective empathy were not more likely to feel the same emotions as the performer. If anything, members with lower cognitive perspective-taking ability had marginally greater emotional overlap with the performer, which makes sense given that these participants were less likely to identify the music as sad, which corresponded with the performer’s actual feelings. Results replicate findings from solo lab studies in a concert setting and demonstrate the viability of exploring empathy and collective cognition in improvised live performance.

Keywords: audience, cognition, collective cognition, emotion, empathy, expressed emotion, felt emotion, improvisation, live performance, recognized emotion

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Authors: Arti Singh, Carolyn Jenkins, Oyedunni S. Arulogun, Mayowa O. Owolabi, Fred S. Sarfo, Bruce Ovbiagele, Enzinne Sylvia

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Background: Stroke, the leading cause of adult-onset disability and the second leading cause of death, is a major public health concern particularly pertinent in Sub-Saharan Africa (SSA), where nearly 80% of all global stroke mortalities occur. The Stroke Investigative Research and Education Network (SIREN) seeks to comprehensively characterize the genomic, sociocultural, economic, and behavioral risk factors for stroke and to build effective teams for research to address and decrease the burden of stroke and other non communicable diseases in SSA. One of the first steps to address this goal was to effectively engage the communities that suffer the high burden of disease in SSA. This study describes how the SIREN project engaged six sites in Ghana and Nigeria over the past three years, describing the community engagement activities that have arisen since inception. Aim: The aim of community engagement (CE) within SIREN is to elucidate information about knowledge, attitudes, beliefs, and practices (KABP) about stroke and its risk factors from individuals of African ancestry in SSA, and to educate the community about stroke and ways to decrease disabilities and deaths from stroke using socioculturally appropriate messaging and messengers. Methods: Community Advisory Board (CABs), Focus Group Discussions (FGDs) and community outreach programs. Results: 27 FGDs with 168 participants including community heads, religious leaders, health professionals and individuals with stroke among others, were conducted, and over 60 CE outreaches have been conducted within the SIREN performance sites. Over 5,900 individuals have received education on cardiovascular risk factors and about 5,000 have been screened for cardiovascular risk factors during the outreaches. FGDs and outreach programs indicate that knowledge of stroke, as well as risk factors and follow-up evidence-based care is limited and often late. Other findings include: 1) Most recognize hypertension as a major risk factor for stroke. 2) About 50% report that stroke is hereditary and about 20% do not know organs affected by stroke. 3) More than 95% willing to participate in genetic testing research and about 85% willing to pay for testing and recommend the test to others. 4) Almost all indicated that genetic testing could help health providers better treat stroke and help scientists better understand the causes of stroke. The CABs provided stakeholder input into SIREN activities and facilitated collaborations among investigators, community members and stakeholders. Conclusion: The CE core within SIREN is a first-of-its kind public outreach engagement initiative to evaluate and address perceptions about stroke and genomics by patients, caregivers, and local leaders in SSA and has implications as a model for assessment in other high-stroke risk populations. SIREN’s CE program uses best practices to build capacity for community-engaged research, accelerate integration of research findings into practice and strengthen dynamic community-academic partnerships within our communities. CE has had several major successes over the past three years including our multi-site collaboration examining the KABP about stroke (symptoms, risk factors, burden) and genetic testing across SSA.

Keywords: community advisory board, community engagement, focus groups, outreach, SSA, stroke

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Authors: Philipp Wenger, Michael Beltle, Stefan Tenbohlen, Uwe Riechert

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The integration of renewable energy introduces new challenges to the transmission grid, as the power generation is located far from load centers. The associated necessary long-range power transmission increases the demand for high voltage direct current (HVDC) transmission lines and DC distribution grids. HVDC gas-insulated switchgears (GIS) are considered being a key technology, due to the combination of the DC technology and the long operation experiences of AC-GIS. To ensure long-term reliability of such systems, insulation defects must be detected in an early stage. Operational experience with AC systems has proven evidence, that most failures, which can be attributed to breakdowns of the insulation system, can be detected and identified via partial discharge (PD) measurements beforehand. In AC systems the identification of defects relies on the phase resolved partial discharge pattern (PRPD). Since there is no phase information within DC systems this method cannot be transferred to DC PD diagnostic. Furthermore, the behaviour of e.g. free-moving particles differs significantly at DC: Under the influence of a constant direct electric field, charge carriers can accumulate on particles’ surfaces. As a result, a particle can lift-off, oscillate between the inner conductor and the enclosure or rapidly bounces at just one electrode, which is known as firefly motion. Depending on the motion and the relative position of the particle to the electrodes, broadband electromagnetic PD pulses are emitted, which can be recorded by ultra-high frequency (UHF) measuring methods. PDs are often accompanied by light emissions at the particle’s tip which enables optical detection. This contribution investigates PD characteristics of free moving metallic particles in a commercially available 300 kV SF6-insulated HVDC-GIS. The influences of various defect parameters on the particle motion and the PD characteristic are evaluated experimentally. Several particle geometries, such as cylinder, lamella, spiral and sphere with different length, diameter and weight are determined. The applied DC voltage is increased stepwise from inception voltage up to UDC = ± 400 kV. Different physical detection methods are used simultaneously in a time-synchronized setup. Firstly, the electromagnetic waves emitted by the particle are recorded by an UHF measuring system. Secondly, a photomultiplier tube (PMT) detects light emission with a wavelength in the range of λ = 185…870 nm. Thirdly, a high-speed camera (HSC) tracks the particle’s motion trajectory with high accuracy. Furthermore, an electrically insulated electrode is attached to the grounded enclosure and connected to a current shunt in order to detect low frequency ion currents: The shunt measuring system’s sensitivity is in the range of 10 nA at a measuring bandwidth of bw = DC…1 MHz. Currents of charge carriers, which are generated at the particle’s tip migrate through the gas gap to the electrode and can be recorded by the current shunt. All recorded PD signals are analyzed in order to identify characteristic properties of different particles. This includes e.g. repetition rates and amplitudes of successive pulses, characteristic frequency ranges and detected signal energy of single PD pulses. Concluding, an advanced understanding of underlying physical phenomena particle motion in direct electric field can be derived.

Keywords: current shunt, free moving particles, high-speed imaging, HVDC-GIS, UHF

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Authors: Scott M. Black, Craig Maclean, Pauline Hall Barrientos, Konstantinos Ritos, Asimina Kazakidi

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Aortic aneurysms and dissections are leading causes of death in cardiovascular disease. Both inevitably lead to hemodynamic instability without surgical intervention in the form of vascular stent-graft deployment. An accurate description of the aortic geometry and blood flow in patient-specific cases is vital for treatment planning and long-term success of such grafts, as they must generate physiological branch perfusion and in-stent hemodynamics. The aim of this study was to create patient-specific computational fluid dynamics (CFD) models through a multi-modality, multi-dimensional approach with boundary condition optimization to predict branch flow rates and in-stent hemodynamics in custom stent-graft configurations. Three-dimensional (3D) thoracoabdominal aortae were reconstructed from four-dimensional flow-magnetic resonance imaging (4D Flow-MRI) and computed tomography (CT) medical images. The former employed a novel approach to generate and enhance vessel lumen contrast via through-plane velocity at discrete, user defined cardiac time steps post-hoc. To produce patient-specific boundary conditions (BCs), the aortic geometry was reduced to a one-dimensional (1D) model. Thereafter, a zero-dimensional (0D) 3-Element Windkessel model (3EWM) was coupled to each terminal branch to represent the distal vasculature. In this coupled 0D-1D model, the 3EWM parameters were optimized to yield branch flow waveforms which are representative of the 4D Flow-MRI-derived in-vivo data. Thereafter, a 0D-3D CFD model was created, utilizing the optimized 3EWM BCs and a 4D Flow-MRI-obtained inlet velocity profile. A sensitivity analysis on the effects of stent-graft configuration and BC parameters was then undertaken using multiple stent-graft configurations and a range of distal vasculature conditions. 4D Flow-MRI granted unparalleled visualization of blood flow throughout the cardiac cycle in both the pre- and postsurgical states. Segmentation and reconstruction of healthy and stented regions from retrospective 4D Flow-MRI images also generated 3D models with geometries which were successfully validated against their CT-derived counterparts. 0D-1D coupling efficiently captured branch flow and pressure waveforms, while 0D-3D models also enabled 3D flow visualization and quantification of clinically relevant hemodynamic parameters for in-stent thrombosis and graft limb occlusion. It was apparent that changes in 3EWM BC parameters had a pronounced effect on perfusion distribution and near-wall hemodynamics. Results show that the 3EWM parameters could be iteratively changed to simulate a range of graft limb diameters and distal vasculature conditions for a given stent-graft to determine the optimal configuration prior to surgery. To conclude, this study outlined a methodology to aid in the prediction post-surgical branch perfusion and in-stent hemodynamics in patient specific cases for the implementation of custom stent-grafts.

Keywords: 4D flow-MRI, computational fluid dynamics, vascular stent-grafts, windkessel

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Authors: Jane Oliver, Angeline Ferdinand, Jessica Kaufman, Peta Edler, Nicole Allard, Margie Danchin, Katherine B. Gibney

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Background: The cohealth Health Concierge program operated in Melbourne, Australia, from July 2020 to 30 June 2022. The program was designed to provide place-based peer-to-peer COVID-19 education and support to culturally and linguistically diverse residents of high-rise public housing estates. During this time, the COVID-19 public health response changed frequently. We conducted a mixed-methods evaluation to determine the program’s impact on residents’ trust, engagement and communication with health services and public health activities. Methods: The RE-AIM model was used to assess program reach, effectiveness, adoption, implementation and maintenance and the evaluation was informed by a Project Reference Group including end-users. Data were collected between March and May 2022 in four estates where the program operated. We surveyed 301 residents, conducted qualitative interviews with 32 stakeholders and analyzed data from 20,901 forms reporting interactions between Health Concierges and residents collected from August 2021 to May 2022. These forms outlined the support provided by Health Concierges during each interaction. Results: Overall, the program was effective in guiding residents to testing and vaccination services and facilitating COVID-19 safe practices. Nearly two-thirds (191; 63.5%) of the 301 surveyed participants reported speaking with a Health Concierge in the previous six months, and some described having meaningful conversations with them. Despite this, many of the interactions residents described having with Health Concierges were superficial. When considering surveyed participants’ responses to the adapted Public Health Disaster Trust Scale, the mean score across all estates was 2.3 (or slightly more than ‘somewhat confident’) in public health authorities’ ability to respond to a localized infectious disease outbreak. While the program was valued during the rapidly changing public health response, many felt it had failed to evolve in the ‘living with COVID’ phase. Some residents expressed frustration with Health Concierges’ having perceived inactive, passive roles - although other residents felt Health Concierges were helpful and appreciated them. A perception that the true impact of Health Concierges’ work was underrecognized was widely voiced by health staff. All 20,901 Interaction Forms identified COVID-19-related supports provided to residents; almost all included provision of facemasks and/or hand sanitiser and 78% identified additional supports that were also provided, most frequently provision of other health information. Conclusions: The program disseminated up-to-date information to a diverse population within a rapidly changing public health setting. Health Concierges were able promote COVID-19-safe behaviours, including vaccine uptake, and link residents with support services. We recommend the program be revised and continued. New programs that draw on the Health Concierge model may be valuable in supporting future pandemic responses and should be considered in preparedness planning.

Keywords: community health, COVID-19 pandemic, infectious diseases, public health, community health workers

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Authors: Alon Cohen, Jeffrey Kantor, Shalom Levy

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The use of the audit risk model in auditing has faced limitations and difficulties, leading auditors to rely on a conceptual level of its application. The qualitative approach to assessing risks has resulted in different risk assessments, affecting the quality of audits and decision-making on the adoption of CAATTs. This study aims to investigate risk factors impacting the implementation of the audit risk model and propose a complementary risk-based instrument (KRIs) to form substance risk judgments and mitigate against heightened risk of material misstatement (RMM). The study addresses the question of how risk factors impact the implementation of the audit risk model, improve risk judgments, and aid in the adoption of CAATTs. The study uses a three-stage scale development procedure involving a pretest and subsequent study with two independent samples. The pretest involves an exploratory factor analysis, while the subsequent study employs confirmatory factor analysis for construct validation. Additionally, the authors test the ability of the KRIs to predict audit efforts needed to mitigate against heightened RMM. Data was collected through two independent samples involving 767 participants. The collected data was analyzed using exploratory factor analysis and confirmatory factor analysis to assess scale validity and construct validation. The suggested KRIs, comprising two risk components and seventeen risk items, are found to have high predictive power in determining audit efforts needed to reduce RMM. The study validates the suggested KRIs as an effective instrument for risk assessment and decision-making on the adoption of CAATTs. This study contributes to the existing literature by implementing a holistic approach to risk assessment and providing a quantitative expression of assessed risks. It bridges the gap between intuitive risk evaluation and the theoretical domain, clarifying the mechanism of risk assessments. It also helps improve the uniformity and quality of risk assessments, aiding audit standard-setters in issuing updated guidelines on CAATT adoption. A few limitations and recommendations for future research should be mentioned. First, the process of developing the scale was conducted in the Israeli auditing market, which follows the International Standards on Auditing (ISAs). Although ISAs are adopted in European countries, for greater generalization, future studies could focus on other countries that adopt additional or local auditing standards. Second, this study revealed risk factors that have a material impact on the assessed risk. However, there could be additional risk factors that influence the assessment of the RMM. Therefore, future research could investigate other risk segments, such as operational and financial risks, to bring a broader generalizability to our results. Third, although the sample size in this study fits acceptable scale development procedures and enables drawing conclusions from the body of research, future research may develop standardized measures based on larger samples to reduce the generation of equivocal results and suggest an extended risk model.

Keywords: audit risk model, audit efforts, CAATTs adoption, key risk indicators, sustainability

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Authors: Yaroslav Pavlov

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In the modern world, ensuring quality has become increasingly important in various fields of human activity. One universal approach to quality management, proven effective in the food industry, is the HACCP (Hazard Analysis and Critical Control Points) concept. Based on principles of preventing potential hazards to consumers at all stages of production, from raw materials to the final product, HACCP offers a systematic approach to identifying, assessing risks, and managing critical control points (CCPs). Initially used primarily for food production, it was later effectively adapted to the food service sector. Implementing HACCP provides organizations with a reliable foundation for improving food safety, covering all links in the food chain from producer to consumer, making it an integral part of modern quality management systems. The main principles of HACCP—hazard identification, CCP determination, effective monitoring procedures, corrective actions, regular checks, and documentation—are universal and can be adapted to other areas. The adaptation of the HACCP concept is relevant for continuing professional education (CPE) with certain reservations. Specifically, it is reasonable to abandon the term ‘hazards’ as deviations in CCPs do not pose dangers, unlike in food production. However, the approach through CCP analysis and the use of HACCP's main principles for educational services are promising. This is primarily because it allows for identifying key CCPs based on the value creation model of a specific educational organization and consequently focusing efforts on specific CCPs to manage the quality of educational services. This methodology can be called the Analysis of Critical Points in Educational Services (ACPES). ACPES offers a similar approach to managing the quality of educational services, focusing on preventing and eliminating potential risks that could negatively impact the educational process, learners' achievement of set educational goals, and ultimately lead to students rejecting the organization's educational services. ACPES adapts proven HACCP principles to educational services, enhancing quality management effectiveness and student satisfaction. ACPES includes identifying potential problems at all stages of the educational process, from initial interest to graduation and career development. In ACPES, the term "hazards" is replaced with "problematic areas," reflecting the specific nature of the educational environment. Special attention is paid to determining CCPs—stages where corrective measures can most effectively prevent or minimize the risk of failing educational goals. The ACPES principles align with HACCP's principles, adjusted for the specificities of CPE. The method of the learner's journey map (variation of Customer Journey Map, CJM) can be used to overcome the complexity of formalizing the production chain in educational services. CJM provides a comprehensive understanding of the learner's experience at each stage, facilitating targeted and effective quality management. Thus, integrating the learner's journey map into ACPES represents a significant extension of the methodology's capabilities, ensuring a comprehensive understanding of the educational process and forming an effective quality management system focused on meeting learners' needs and expectations.

Keywords: quality management, continuing professional education, customer journey map, HACCP

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Authors: Eric Bang

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Interactions between receptors and ligands are crucial for many essential biological processes, including neurotransmission and metabolism. Ligand-receptor analyses that examine cell behavior and interactions often utilize cell type-specific RNA expressions from single-cell RNA sequencing (scRNA-seq) data. Using CellPhoneDB, a public repository consisting of ligands, receptors, and ligand-receptor interactions, the cell-cell interactions were explored in a specific scRNA-seq dataset from kidney tissue and portrayed the results with dot plots and heat maps. Depending on the type of cell, each ligand-receptor pair was aligned with the interacting cell type and calculated the positori probabilities of these associations, with corresponding P values reflecting average expression values between the triads and their significance. Using single-cell data (sample kidney cell references), genes in the dataset were cross-referenced with ones in the existing CellPhoneDB dataset. For example, a gene such as Pleiotrophin (PTN) present in the single-cell data also needed to be present in the CellPhoneDB dataset. Using the single-cell transcriptomics data via slide-seq and reference data, the CellPhoneDB program defines cell types and plots them in different formats, with the two main ones being dot plots and heat map plots. The dot plot displays derived measures of the cell to cell interaction scores and p values. For the dot plot, each row shows a ligand-receptor pair, and each column shows the two interacting cell types. CellPhoneDB defines interactions and interaction levels from the gene expression level, so since the p-value is on a -log10 scale, the larger dots represent more significant interactions. By performing an interaction analysis, a significant interaction was discovered for myeloid and T-cell ligand-receptor pairs, including those between Secreted Phosphoprotein 1 (SPP1) and Fibronectin 1 (FN1), which is consistent with previous findings. It was proposed that an effective protocol would involve a filtration step where cell types would be filtered out, depending on which ligand-receptor pair is activated in that part of the tissue, as well as the incorporation of the CellPhoneDB data in a streamlined workflow pipeline. The filtration step would be in the form of a Python script that expedites the manual process necessary for dataset filtration. Being in Python allows it to be integrated with the CellPhoneDB dataset for future workflow analysis. The manual process involves filtering cell types based on what ligand/receptor pair is activated in kidney cells. One limitation of this would be the fact that some pairings are activated in multiple cells at a time, so the manual manipulation of the data is reflected prior to analysis. Using the filtration script, accurate sorting is incorporated into the CellPhoneDB database rather than waiting until the output is produced and then subsequently applying spatial data. It was envisioned that this would reveal wherein the cell various ligands and receptors are interacting with different cell types, allowing for easier identification of which cells are being impacted and why, for the purpose of disease treatment. The hope is this new computational method utilizing spatially explicit ligand-receptor association data can be used to uncover previously unknown specific interactions within kidney tissue.

Keywords: bioinformatics, Ligands, kidney tissue, receptors, spatial transcriptome

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Authors: Sami El Khatib, Agnès Leroux, Jean-Louis Merlin, François Guillemin, Marie-Ange D’Hallewin

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Photodynamic therapy (PDT) is a treatment modality based on the cytotoxic effect occurring on the target tissues by interaction of a photosensitizer with light in the presence of oxygen. One of the major advances in PDT can be attributed to the use of topical aminolevulinic (ALA) to induce Protoporphyrin IX (PpIX) for the treatment of early stage cancers as well as diagnosis. ALA is a precursor of the heme synthesis pathway. Locally delivered to the target tissue ALA overcomes the negative feedback exerted by heme and promotes the transient formation of PpIX in situ to reach critical effective levels in cells and tissue. Whereas early steps of the heme pathway occur in the cytosol, PpIX synthesis is shown to be held in the mitochondrial membranes and PpIX fluorescence is expected to accumulate in close vicinity of the initial building site and to progressively diffuse to the neighboring cytoplasmic compartment or other lipophylic organelles. PpIX is known to be highly reactive and will be degraded when irradiated with light. PpIX photobleaching is believed to be governed by a singlet oxygen mediated mechanism in the presence of oxidized amino acids and proteins. PpIX photobleaching and subsequent spectral phototransformation were described widely in tumor cells incubated in vitro with ALA solution, or ex vivo in human and porcine mucosa superfused with hexylaminolevulinate (hALA). PpIX photobleaching was also studied in vivo, using animal models such as normal or tumor mice skin and orthotopic rat bladder model. Hexyl aminolevulinate a more potent lipophilic derivative of ALA was proposed as an adjunct to standard cystoscopy in the fluorescence diagnosis of bladder cancer and other malignancies. We have previously reported the effectiveness of hALA mediated PDT of rat bladder cancer. Although normal and tumor bladder epithelium exhibit similar fluorescence intensities after intravesical instillation of two hALA concentrations (8 and 16 mM), the therapeutic response at 8mM and 20J/cm2 was completely different from the one observed at 16mM irradiated with the same light dose. Where the tumor is destroyed, leaving the underlying submucosa and muscle intact after an 8 mM instillation, 16mM sensitization and subsequent illumination results in the complete destruction of the underlying bladder wall but leaves the tumor undamaged. The object of the current study is to try to unravel the underlying mechanism for this apparent contradiction. PpIX extraction showed identical amounts of photosensitizer in tumor bearing bladders at both concentrations. Photobleaching experiments revealed mono-exponential decay curves in both situations but with a two times faster decay constant in case of 16mM bladders. Fluorescence microscopy shows an identical fluorescence pattern for normal bladders at both concentrations and tumor bladders at 8mM with bright spots. Tumor bladders at 16 mM exhibit a more diffuse cytoplasmic fluorescence distribution. The different response to PDT with regard to the initial pro-drug concentration can thus be attributed to the different cellular localization.

Keywords: bladder cancer, hexyl-aminolevulinate, photobleaching, confocal fluorescence microscopy

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Authors: Natalia Hordynska, Magdalena Szechynska-Hebda, Miroslaw Sobczak, Elzbieta Rozanska, Joanna Troczynska, Zofia Banaszak, Maria Wedzony

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Albinism is a common problem encountered in wheat and triticale breeding programs, which require in vitro culture steps e.g. generation of doubled haploids via androgenesis process. Genetic factor is a major determinant of albinism, however, environmental conditions such as temperature and media composition influence the frequency of albino plant formation. Cold incubation of wheat and triticale spikes induced a switch from gametophytic to sporophytic development. Further, androgenic structures formed from anthers of the genotypes susceptible to androgenesis or treated with cold stress, had a pool of structurally primitive plastids, with small starch granules or swollen thylakoids. High temperature was a factor inducing andro-genesis of wheat and triticale, but at the same time, it was a factor favoring the formation of albino plants. In genotypes susceptible to albinism or after heat stress conditions, cells formed from anthers were vacuolated, and plastids were eliminated. Partial or complete loss of chlorophyll pigments and incomplete differentiation of chloroplast membranes result in formation of tissues or whole plant unable to perform photosynthesis. Indeed, susceptibility to the andro-genesis process was associated with an increase of total concentration of photosynthetic pigments in anthers, spikes and regenerated plants. The proper balance of the synthesis of various pigments, was the starting point for their proper incorporation into photosynthetic membranes. In contrast, genotypes resistant to the androgenesis process and those treated with heat, contained 100 times lower content of photosynthetic pigments. In particular, the synthesis of violaxanthin, zeaxanthin, lutein and chlorophyll b was limited. Furthermore, deregulation of starch and lipids synthesis, which led to the formation of very complex starch granules and an increased number of oleosomes, respectively, correlated with the reduction of the efficiency of androgenesis. The content of other sugars varied depending on the genotype and the type of stress. The highest content of various sugars was found for genotypes susceptible to andro-genesis, and highly reduced for genotypes resistant to androgenesis. The most important sugars seem to be glucose and fructose. They are involved in sugar sensing and signaling pathways, which affect the expression of various genes and regulate plant development. Sucrose, on the other hand, seems to have minor effect at each stage of the androgenesis. The sugar metabolism was related to metabolic activity of microspores. The genotypes susceptible to androgenesis process had much faster mitochondrium- and chloroplast-dependent energy conversion and higher heat production by tissues. Thus, the effectiveness of metabolic processes, their balance and the flexibility under the stress was a factor determining the direction of microspore development, and in the later stages of the androgenesis process, a factor supporting the induction of androgenic structures, chloroplast formation and the regeneration of green plants. The work was financed by Ministry of Agriculture and Rural Development within Program: ‘Biological Progress in Plant Production’, project no HOR.hn.802.15.2018.

Keywords: androgenesis, chloroplast, metabolism, temperature stress

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Authors: Emma J. Dale, Christina D. Buesching, Kevin R. Theis, David W. Macdonald

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This study investigates the oral and intestinal microbiomes of wild-living European badgers (Meles meles) and will relate inter-individual differences to social contact networks, somatic and reproductive fitness, varying susceptibility to bovine tuberculous (bTB) and to the olfactory advertisement. Badgers are an interesting model for this research, as they have great variation in body condition, despite living in complex social networks and having access to the same resources. This variation in somatic fitness, in turn, affects breeding success, particularly in females. We postulate that microbiota have a central role to play in determining the successfulness of an individual. Our preliminary results, characterising the microbiota of individual badgers, indicate unique compositions of microbiota communities within social groups of badgers. This basal information will inform further questions related to the extent microbiota influence fitness. Hitherto, the potential role of microbiota has not been considered in determining host condition, but also other key fitness variables, namely; communication and resistance to disease. Badgers deposit their faeces in communal latrines, which play an important role in olfactory communication. Odour profiles of anal and subcaudal gland secretions are highly individual-specific and encode information about group-membership and fitness-relevant parameters, and their chemical composition is strongly dependent on symbiotic microbiota. As badgers sniff/ lick (using their Vomeronasal organ) and over-mark faecal deposits of conspecifics, these microbial communities can be expected to vary with social contact networks. However, this is particularly important in the context of bTB, where badgers are assumed to transmit bTB to cattle as well as conspecifics. Interestingly, we have found that some individuals are more susceptible to bTB than are others. As acquired immunity and thus potential susceptibility to infectious diseases are known to depend also on symbiotic microbiota in other members of the mustelids, a role of particularly oral microbiota can currently not be ruled out as a potential explanation for inter-individual differences in infection susceptibility of bTB in badgers. Tri annually badgers are caught in the context of a long-term population study that began in 1987. As all badgers receive an individual tattoo upon first capture, age, natal as well as previous and current social group-membership and other life history parameters are known for all animals. Swabs (subcaudal ‘scent gland’, anal, genital, nose, mouth and ear) and fecal samples will be taken from all individuals, stored at -80oC until processing. Microbial samples will be processed and identified at Wayne State University’s Theis (Host-Microbe Interactions) Lab, using High Throughput Sequencing (16S rRNA-encoding gene amplification and sequencing). Acknowledgments: Gas-Chromatography/ Mass-spectrometry (in the context of olfactory communication) analyses will be performed through an established collaboration with Dr. Veronica Tinnesand at Telemark University, Norway.

Keywords: communication, energetics, fitness, free-ranging animals, immunology

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Authors: Sujoy Khan

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There is a rising concern with increasing allergies affecting both adults and children in rural and urban India. Recent report on adults in a densely populated North Indian city showed sensitization rates for house dust mite, parthenium, and cockroach at 60%, 40% and 18.75% that is now comparable to allergy prevalence in cities in the United States. Data from patients residing in the eastern part of India is scarce. A retrospective study (over 2 years) was done on patients with allergic rhinitis and asthma where allergen-specific IgE levels were measured to see the aero-allergen sensitization pattern in a large metropolitan city of East India. Total IgE and allergen-specific IgE levels were measured using ImmunoCAP (Phadia 100, Thermo Fisher Scientific, Sweden) using region-specific aeroallergens: Dermatophagoides pteronyssinus (d1); Dermatophagoides farinae (d2); cockroach (i206); grass pollen mix (gx2) consisted of Cynodon dactylon, Lolium perenne, Phleum pratense, Poa pratensis, Sorghum halepense, Paspalum notatum; tree pollen mix (tx3) consisted of Juniperus sabinoides, Quercus alba, Ulmus americana, Populus deltoides, Prosopis juliflora; food mix 1 (fx1) consisted of Peanut, Hazel nut, Brazil nut, Almond, Coconut; mould mix (mx1) consisted of Penicillium chrysogenum, Cladosporium herbarum, Aspergillus fumigatus, Alternaria alternate; animal dander mix (ex1) consisted of cat, dog, cow and horse dander; and weed mix (wx1) consists of Ambrosia elatior, Artemisia vulgaris, Plantago lanceolata, Chenopodium album, Salsola kali, following manufacturer’s instructions. As the IgE levels were not uniformly distributed, median values were used to represent the data. 92 patients with allergic rhinitis and asthma (united airways disease) were studied over 2 years including 21 children (age < 12 years) who had total IgE and allergen-specific IgE levels measured. The median IgE level was higher in 2016 than in 2015 with 60% of patients (adults and children) being sensitized to house dust mite (dual positivity for Dermatophagoides pteronyssinus and farinae). Of 11 children in 2015, whose total IgE ranged from 16.5 to >5000 kU/L, 36% of children were polysensitized (≥4 allergens), and 55% were sensitized to dust mites. Of 10 children in 2016, total IgE levels ranged from 37.5 to 2628 kU/L, and 20% were polysensitized with 60% sensitized to dust mites. Mould sensitivity was 10% in both of the years in the children studied. A consistent finding was that ragweed sensitization (molecular homology to Parthenium hysterophorus) appeared to be increasing across all age groups, and throughout the year, as reported previously by us where 25% of patients were sensitized. In the study sample overall, sensitizations to dust mite, cockroach, and parthenium were important risks in our patients with moderate to severe asthma that reinforces the importance of controlling indoor exposure to these allergens. Sensitizations to dust mite, cockroach and parthenium allergens are important predictors of asthma morbidity not only among children but also among adults in Eastern India.

Keywords: aAeroallergens, asthma, dust mite, parthenium, rhinitis

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Authors: Oyvind Nordvik, Peder O. L. Heggdal, Jonas Brannstrom, Flemming Vassbotn, Anne Kari Aarstad, Hans Jorgen Aarstad

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Background: Hearing Loss (HL) is a condition that may affect people in all stages of life, but the prevalence increases with age, mostly because of age-related HL, generally referred to as presbyacusis. As human speech is related to relatively high frequencies, even a limited hearing loss at high frequencies may cause impaired speech intelligibility. Being diagnosed with, treated for and living with a chronic condition such as HL, must for many be a disabling and stressful condition that put ones coping resources to test. Stress is a natural part of life and most people will experience stressful events or periods. Chronic diseases, such as HL, are risk factor for distress in individuals, causing anxiety and lowered mood. How an individual cope with HL may be closely connected to the level of distress he or she is experiencing and to personality, which can be defined as those characteristics of a person that account for consistent patterns of feelings, thinking, and behavior. Thus, as to distress in life, such as illness or disease, available coping strategies may be more important than the challenge itself. The same line of arguments applies to level of experienced health-related quality of life (HRQoL). Aim: The aim of this study was to investigate the relationship between distress, HRQoL, reported hearing loss, personality and coping in patients with HL. Method: 158 adult (aged 18-78 years) patients with HL, referred for hearing aid (HA) fitting at Haukeland University Hospital in western Norway, participated in the study. Both first-time users, as well as patients referred for HA renewals were included. First-time users had been pre-examined by an ENT-specialist. The questionnaires were answered before the actual HA fitting procedure. The pure-tone average (PTA; frequencies 0.5, 1, 2, and 4 kHz) was determined for each ear. The Eysenck personality inventory, neuroticism and lie scales, the Theoretically Originated Measure of the Cognitive Activation Theory of Stress (TOMCATS) measuring active coping, hopelessness and helplessness, as well as distress (General Health Questionnaire (GHQ) - 12 items) and the EORTC Quality of Life Questionnaire general part were answered. In addition, we used a revised and shortened version of the Abbreviated Profile of Hearing Aid Benefit (APHAB) as a measure of patient-reported hearing loss. Results: Significant correlations were determined between APHAB (weak), HRQoL scores (strong), distress scores (strong) on the one side and personality and choice of coping scores on the other side. As measured by stepwise regression analyses, the distress and HRQoL scores were scored secondary to the obtained personality and coping scores. The APHAB scores were as determined by regression analyses scored secondary to PTA (best ear), level of neuroticism and lie score. Conclusion: We found that reported employed coping style, distress/HRQoL and personality are closely connected to each other in this patient group. Patient-reported HL was associated to hearing level and personality. There is need for further investigations on these questions, and how these associations may influence the clinical context.

Keywords: coping, distress, hearing loss, personality

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Authors: Iryna Teslenko

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According to the provisions of the current criminal procedural legislation of Ukraine, the issue of admissibility of evidence is closely related to both the right to a fair trial and the presumption of innocence. The general rule is that evidence obtained improperly or illegally cannot be taken into account in a court case. Therefore, the evidence base of the prosecution, collected at the stage of the pre-trial investigation, compliance with the requirements of the law during the collection of evidence, is of crucial importance for the criminal process, the violation of which entails the recognition of the relevant evidence as inadmissible, which can nullify all the efforts of the pre-trial investigation body and the prosecution. Therefore, the issue of admissibility of evidence in criminal proceedings is fundamentally important and decisive for the entire process. Research on this issue began in December 2021. At that time, there was still no clear understanding of what needed to be conveyed to the scientific community. In February 2022, the lives of all citizens of Ukraine have totally changed. A war broke out in the country. At a time when the entire world community is on the path of humanizing society, respecting the rights and freedoms of man and citizen, a military conflict has arisen in the middle of Europe - one country attacked another, war crimes are being committed. The world still cannot believe it, but it is happening here and now, people are dying, infrastructure is being destroyed, war crimes are being committed, contrary to the signed and ratified international conventions, and contrary to all the acquisitions and development of world law. At this time, the life of the world has divided into before and after February 24, 2022, the world cannot be the same as it was before, and the approach to solving legal issues in the criminal process, in particular, issues of proving the commission of crimes and the involvement of certain persons in their commission. An international criminal has appeared in the humane European world, who disregards all norms of law and morality, and does not adhere to any principles. Until now, the practice of the European Court of Human Rights and domestic courts of Ukraine treated with certain formalism, such a property of evidence in criminal proceedings as the admissibility of evidence. Currently, we have information that the Office of the Prosecutor of the International Criminal Court in The Hague has started an investigation into war crimes in Ukraine and is documenting them. In our opinion, the world cannot allow formalism in bringing a war criminal to justice. There is a war going on in Ukraine, the cities are under round-the-clock missile fire from the aggressor country, which makes it impossible to carry out certain investigative actions. If due to formal deficiencies, the collected evidence is declared inadmissible, it may lead to the fact that the guilty people will not be punished. And this, in turn, sends a message to other terrorists in the world about the impunity of their actions, the system of deterring criminals from committing criminal offenses (crimes) will collapse due to the understanding of the inevitability of punishment, and this will affect the entire world security and European security in particular. Therefore, we believe that the world cannot allow chaos in the issue of general security, there should be a transformation of the approach in general to such a property of evidence in the criminal process as admissibility in order to ensure the inevitability of the punishment of criminals. We believe that the scientific and legal community should not allow criminals to avoid responsibility. The evil that is destroying Ukraine should be punished. We must all together prove that legal norms are not just words written on paper but rules of behavior of all members of society, their non-observance leads to mandatory responsibility. Everybody who commits crimes will be punished, which is inevitable, and this principle is the guarantor of world security in the future.

Keywords: admissibility of evidence, criminal process, war, Ukraine

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Authors: Sandeep Kumar Agrawal, Aditi Bhattacharya, Janvie Manhas, Krushna Bhatt, Yatin Kholakiya, Nupur Khera, Ajoy Roychoudhury, Sudip Sen

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Autologous cultured explants of human oral mucosal epithelial cells (OMEC) are a potential therapeutic modality for limbal stem cell deficiency (LSCD). Injury or inflammation of the ocular surface in the form of burns, chemicals, Stevens Johnson syndrome, ocular cicatricial pemphigoid etc. can lead to destruction and deficiency of limbal stem cells. LSCD manifests in the form of severe ocular surface diseases (OSD) characterized by persistent and recurrent epithelial defects, conjuntivalisation and neovascularisation of the corneal surface, scarring and ultimately opacity and blindness. Most of the cases of OSD are associated with severe dry eye pertaining to diminished mucin and aqueous secretion. Mycophenolate mofetil (MMF) has been shown to upregulate the mucin expression in conjunctival goblet cells in vitro. The aim of this study was to evaluate the effects of MMF on mucin expression in primary cultures of oral mucosal epithelial cells. With institutional ethics committee approval and written informed consent, thirty oral mucosal epithelial tissue samples were obtained from patients undergoing oral surgery for non-malignant conditions. OMEC were grown on human amniotic membrane (HAM, obtained from expecting mothers undergoing elective caesarean section) scaffold for 2 weeks in growth media containing DMEM & Ham’s F12 (1:1) with 10% FBS and growth factors. In vitro dosage of MMF was standardised by MTT assay. Analysis of stem cell markers was done using RT-PCR while mucin mRNA expression was quantified using RT-PCR and q-PCR before and after treating cultured OMEC with graded concentrations of MMF for 24 hours. Protein expression was validated using immunocytochemistry. Morphological studies revealed a confluent sheet of proliferating, stratified oral mucosal epithelial cells growing over the surface of HAM scaffold. The presence of progenitor stem cell markers (p63, p75, β1-Integrin and ABCG2) and cell surface associated mucins (MUC1, MUC15 and MUC16) were elucidated by RT-PCR. The mucin mRNA expression was found to be upregulated in MMF treated primary cultures of OMEC, compared to untreated controls as quantified by q-PCR with β-actin as internal reference gene. Increased MUC1 protein expression was validated by immunocytochemistry on representative samples. Our findings conclude that OMEC have the ability to form a multi-layered confluent sheet on the surface of HAM similar to a cornea, which is important for the reconstruction of the damaged ocular surface. Cultured OMEC has stem cell properties as demonstrated by stem cell markers. MMF can be a novel enhancer of mucin production in OMEC. It has the potential to improve dry eye in patients undergoing OMEC transplantation for bilateral OSD. Further clinical trials are required to establish the role of MMF in patients undergoing OMEC transplantation.

Keywords: limbal stem cell deficiency, mycophenolate mofetil, mucin, ocular surface disease

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Authors: Arzyana Sunkar, Yanto Santosa, Siti Badriyah Rushayati

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Indonesia has experienced annual forest fires that have rapidly destroyed and degraded its forests. Fires in the peat swamp forests of Riau Province, have set the stage for problems to worsen, this being the ecosystem most prone to fires (which are also the most difficult, to extinguish). Despite various efforts to curb deforestation, and forest degradation processes, severe forest fires are still occurring. To find an effective solution, the basic causes of the problems must be identified. It is therefore critical to have an in-depth understanding of the underlying causal factors that have contributed to deforestation and forest degradation as a whole, in order to attain reductions in their rates. An assessment of the drivers of deforestation and forest degradation was carried out, in order to design and implement measures that could slow these destructive processes. Research was conducted in Giam Siak Kecil–Bukit Batu Biosphere Reserve (GSKBB BR), in the Riau Province of Sumatera, Indonesia. A biosphere reserve was selected as the study site because such reserves aim to reconcile conservation with sustainable development. A biosphere reserve should promote a range of local human activities, together with development values that are in line spatially and economically with the area conservation values, through use of a zoning system. Moreover, GSKBB BR is an area with vast peatlands, and is experiencing forest fires annually. Various factors were analysed to assess the drivers of deforestation and forest degradation in GSKBB BR; data were collected from focus group discussions with stakeholders, key informant interviews with key stakeholders, field observation and a literature review. Landsat satellite imagery was used to map forest-cover changes for various periods. Analysis of landsat images, taken during the period 2010-2014, revealed that within the non-protected area of core zone, there was a trend towards decreasing peat swamp forest areas, increasing land clearance, and increasing areas of community oil-palm and rubber plantations. Fire was used for land clearing and most of the forest fires occurred in the most populous area (the transition area). The study found a relationship between the deforested/ degraded areas, and certain distance variables, i.e. distance from roads, villages and the borders between the core area and the buffer zone. The further the distance from the core area of the reserve, the higher was the degree of deforestation and forest degradation. Research findings suggested that agricultural expansion may be the direct cause of deforestation and forest degradation in the reserve, whereas socio-economic factors were the underlying driver of forest cover changes; such factors consisting of a combination of socio-cultural, infrastructural, technological, institutional (policy and governance), demographic (population pressure) and economic (market demand) considerations. These findings indicated that local factors/problems were the critical causes of deforestation and degradation in GSKBB BR. This research therefore concluded that reductions in deforestation and forest degradation in GSKBB BR could be achieved through ‘local actor’-tailored approaches such as community empowerment

Keywords: Actor-led solution, community empowerment, drivers of deforestation and forest degradation, Giam Siak Kecil – Bukit Batu Biosphere Reserve

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Authors: Sahar Nasr, Lin Li, Edwin Wang

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Bladder cancer (BLCA) is known as the 13th cause of death among cancer patients worldwide, and ~575,000 new BLCA cases are diagnosed each year. Urothelial carcinoma (UC) is the most prevalent subtype among BLCA patients, which can be categorized into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Currently, various therapeutic options are available for UC patients, including (1) transurethral resection followed by intravesical instillation of chemotherapeutics or Bacillus Calmette-Guérin for NMIBC patients, (2) neoadjuvant platinum-based chemotherapy (NAC) plus radical cystectomy is the standard of care for localized MIBC patients, and (3) systematic chemotherapy for metastatic UC. However, conventional treatments may lead to several challenges for treating patients. As an illustration, some patients may suffer from recurrence of the disease after the first line of treatment. Recently, immune checkpoint therapy (ICT) has been introduced as an alternative treatment strategy for the first or second line of treatment in advanced or metastatic BLCA patients. Although ICT showed lucrative results for a fraction of BLCA patients, ~80% of patients were not responsive to it. Therefore, novel treatment methods are required to augment the ICI response rate within BLCA patients. It has been shown that the infiltration of T-cells into the tumor microenvironment (TME) is positively correlated with the response to ICT within cancerous patients. Therefore, the goal of this study is to enhance the infiltration of cytotoxic T-cells into TME through the identification of target genes within the tumor that are responsible for the non-T-cell inflamed TME and their inhibition. BLCA bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and immune score for TCGA samples were used to determine the Pearson correlation score between the expression of different genes and immune score for each sample. The genes with strong negative correlations were selected (r < -0.2). Thereafter, the correlation between the expression of each gene and survival in BLCA patients was calculated using the TCGA data and Cox regression method. The genes that are common in both selected gene lists were chosen for further analysis. Afterward, BLCA bulk and single-cell RNA-sequencing data were ranked based on the expression of each selected gene and the top and bottom 25% samples were used for pathway enrichment analysis. If the pathways related to the T-cell infiltration (e.g., antigen presentation, interferon, or chemokine pathways) were enriched within the low-expression group, the gene was included for downstream analysis. Finally, the selected genes will be used to calculate the correlation between their expression and the infiltration rate of the activated CD+8 T-cells, natural killer cells and the activated dendric cells. A list of potential target genes has been identified and ranked based on the above-mentioned analysis and criteria. SUN-1 got the highest score within the gene list and other identified genes in the literature as benchmarks. In conclusion, inhibition of SUN1 may increase the tumor-infiltrating lymphocytes and the efficacy of ICI in BLCA patients. BLCA tumor cells with and without SUN-1 CRISPR/Cas9 knockout will be injected into the syngeneic mouse model to validate the predicted SUN-1 effect on increasing tumor-infiltrating lymphocytes.

Keywords: data analysis, gene expression analysis, gene identification, immunoinformatic, functional genomics, transcriptomics

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Authors: Yagmur Soylu, Emir Ozeren, Erol Esen, Digdem M. Siyez, Ozlem Belkis, Ezgi Burc, Gülce Demirgurz

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The aim of the study is to determine the predictive power of personal growth initiative, socio-demographic variables (such as sex, grade, and working condition) on career adaptability and optimism of bachelor students in Dokuz Eylul University in Turkey. According to career construction theory, career adaptability is viewed as a psychosocial construct, which refers to an individual’s resources for dealing with current and expected tasks, transitions and traumas in their occupational roles. Career optimism is defined as positive results for future career development of individuals in the expectation that it will achieve or to put the emphasis on the positive aspects of the event and feel comfortable about the career planning process. Personal Growth Initiative (PGI) is defined as being proactive about one’s personal development. Additionally, personal growth is defined as the active and intentional engagement in the process of personal. A study conducted on college students revealed that individuals with high self-development orientation make more effort to discover the requirements of the profession and workspaces than individuals with low levels of personal development orientation. University life is a period that social relations and the importance of academic activities are increased, the students make efforts to progress through their career paths and it is also an environment that offers opportunities to students for their self-realization. For these reasons, personal growth initiative is potentially an important variable which has a key role for an individual during the transition phase from university to the working life. Based on the review of the literature, it is expected that individual’s personal growth initiative, sex, grade, and working condition would significantly predict one’s career adaptability. In the relevant literature, it can be seen that there are relatively few studies available on the career adaptability and optimism of university students. Most of the existing studies have been carried out with limited respondents. In this study, the authors aim to conduct a comprehensive research with a large representative sample of bachelor students in Dokuz Eylul University, Izmir, Turkey. By now, personal growth initiative and career development constructs have been predominantly discussed in western contexts where individualistic tendencies are likely to be seen. Thus, the examination of the same relationship within the context of Turkey where collectivistic cultural characteristics can be more observed is expected to offer valuable insights and provide an important contribution to the literature. The participants in this study were comprised of 1500 undergraduate students being included from thirteen faculties in Dokuz Eylul University. Stratified and random sampling methods were adopted for the selection of the participants. The Personal Growth Initiative Scale-II and Career Futures Inventory were used as the major measurement tools. In data analysis stage, several statistical analysis concerning the regression analysis, one-way ANOVA and t-test will be conducted to reveal the relationships of the constructs under investigation. At the end of this project, we will be able to determine the level of career adaptability and optimism of university students at varying degrees so that a fertile ground is likely to be created to carry out several intervention techniques to make a contribution to an emergence of a healthier and more productive youth generation in psycho-social sense.

Keywords: career optimism, career adaptability, personal growth initiative, university students

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Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

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Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

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Authors: Bukra Kalayci, Geraldine Brennan

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Introduction: Over the last decade, a proliferation of literature related to textile and fashion business in the context of sustainable production and consumption has emerged. However, the economic and environmental benefits of solid waste recovery have not been comprehensively searched. Therefore at the end-of-life or end-of-use textile waste management remains a gap. Solid textile waste reuse and recycling principles of the circular economy need to be developed to close the disposal stage of the textile supply chain. The environmental problems associated with the over-production and –consumption of textile products arise. Together with growing population and fast fashion culture the share of solid textile waste in municipal waste is increasing. Focusing on post-consumer textile waste literature, this research explores the opportunities, obstacles and enablers or success factors associated with closed-loop textile business systems. Methodology: A systematic literature review was conducted in order to identify best practices and gaps from the existing body of knowledge related to closed-loop post-consumer textile waste initiatives over the last decade. Selected keywords namely: ‘cradle-to-cradle ‘, ‘circular* economy* ‘, ‘closed-loop* ‘, ‘end-of-life* ‘, ‘reverse* logistic* ‘, ‘take-back* ‘, ‘remanufacture* ‘, ‘upcycle* ‘ with the combination of (and) ‘fashion* ‘, ‘garment* ‘, ‘textile* ‘, ‘apparel* ‘, clothing* ‘ were used and the time frame of the review was set between 2005 to 2017. In order to obtain a broad coverage, Web of Knowledge and Science Direct databases were used, and peer-reviewed journal articles were chosen. The keyword search identified 299 number of papers which was further refined into 54 relevant papers that form the basis of the in-depth thematic analysis. Preliminary findings: A key finding was that the existing literature is predominantly conceptual rather than applied or empirical work. Moreover, the enablers or success factors, obstacles and opportunities to implement closed-loop systems in the textile industry were not clearly articulated and the following considerations were also largely overlooked in the literature. While the circular economy suggests multiple cycles of discarded products, components or materials, most research has to date tended to focus on a single cycle. Thus the calculations of environmental and economic benefits of closed-loop systems are limited to one cycle which does not adequately explore the feasibility or potential benefits of multiple cycles. Additionally, the time period textile products spend between point of sale, and end-of-use/end-of-life return is a crucial factor. Despite past efforts to study closed-loop textile systems a clear gap in the literature is the lack of a clear evaluation framework which enables manufacturers to clarify the reusability potential of textile products through consideration of indicators related too: quality, design, lifetime, length of time between manufacture and product return, volume of collected disposed products, material properties, and brand segment considerations (e.g. fast fashion versus luxury brands).

Keywords: circular fashion, closed loop business, product service systems, solid textile waste elimination

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Authors: Nadia Obaed, Lexi Frankel, Amalia Ardeljan, Denis Nigel, Anniki Witter, Omar Rashid

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Breast cancer is the most common cancer among women, with a lifetime risk of one in eight of all women in the United States. Although breast cancer is prevalent throughout the world, the uneven distribution in incidence and mortality rates is shaped by the variation in population structure, environment, genetics and known lifestyle risk factors. Furthermore, the bacterial profile in healthy and cancerous breast tissue differs with a higher relative abundance of bacteria capable of causing DNA damage in breast cancer patients. Previous bacterial infections may change the composition of the microbiome and partially account for the environmental factors promoting breast cancer. One study found that higher amounts of Staphylococcus, Bacillus, and Enterobacteriaceae, of which Escherichia coli (E. coli) is a part, were present in breast tumor tissue. Based on E. coli’s ability to damage DNA, it is hypothesized that there is an increased risk of breast cancer associated with previous E. coli infection. Therefore, the purpose of this study was to evaluate the correlation between E. coli infection and the incidence of breast cancer. Holy Cross Health, Fort Lauderdale, provided access to the Health Insurance Portability and Accountability (HIPAA) compliant national database for the purpose of academic research. International Classification of Disease 9th and 10th Codes (ICD-9, ICD-10) was then used to conduct a retrospective analysis using data from January 2010 to December 2019. All breast cancer diagnoses and all patients infected versus not infected with E. coli that underwent typical E. coli treatment were investigated. The obtained data were matched for age, Charlson Comorbidity Score (CCI score), and antibiotic treatment. Standard statistical methods were applied to determine statistical significance and an odds ratio was used to estimate the relative risk. A total of 81286 patients were identified and analyzed from the initial query and then reduced to 31894 antibiotic-specific treated patients in both the infected and control group, respectively. The incidence of breast cancer was 2.51% and present in 2043 patients in the E. coli group compared to 5.996% and present in 4874 patients in the control group. The incidence of breast cancer was 3.84% and present in 1223 patients in the treated E. coli group compared to 6.38% and present in 2034 patients in the treated control group. The decreased incidence of breast cancer in the E. coli and treated E. coli groups was statistically significant with a p-value of 2.2x10-16 and 2.264x10-16, respectively. The odds ratio in the E. coli and treated E. coli groups was 0.784 and 0.787 with a 95% confidence interval, respectively (0.756-0.813; 0.743-0.833). The current study shows a statistically significant decrease in breast cancer incidence in association with previous Escherichia coli infection. Researching the relationship between single bacterial species is important as only up to 10% of breast cancer risk is attributable to genetics, while the contribution of environmental factors including previous infections potentially accounts for a majority of the preventable risk. Further evaluation is recommended to assess the potential and mechanism of E. coli in decreasing the risk of breast cancer.

Keywords: breast cancer, escherichia coli, incidence, infection, microbiome, risk

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Authors: Malla Vijayeta, Y. Vijaya Kumar, N. Ramakrishna Raju, K. Satyanarayana

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Global AEC (architecture, engineering, and construction) industry has been coined as one of the most resistive domains in embracing technology. Although this digital era has been inundated with software tools like CAD, STADD, CANDY, Microsoft Project, Primavera etc. the key stakeholders have been working in siloes and processes remain fragmented. Unlike the yesteryears’ simpler project delivery methods, the current projects are of fast-track, complex, risky, multidisciplinary, stakeholder’s influential, statutorily regulative etc. pose extensive bottlenecks in preventing timely completion of projects. At this juncture, a paradigm shift surfaced in construction industry, and Building Information Modeling, aka BIM, has been a panacea to bolster the multidisciplinary teams’ cooperative and collaborative work leading to productive, sustainable and leaner project outcome. Building information modeling has been integrative, stakeholder engaging and centralized approach in providing a common platform of communication. A common misconception that BIM can be used for building/high rise projects in Indian Construction Industry, while this paper discusses of the implementation of BIM processes/methodologies in water and waste water industry. It elucidates about BIM 4D planning and constructability reviews of a Sewage Treatment Plant in India. Conventional construction planning and logistics management involves a blend of experience coupled with imagination. Even though the excerpts or judgments or lessons learnt gained from veterans might be predictive and helpful, but the uncertainty factor persists. This paper shall delve about the case study of real time implementation of BIM 4D planning protocols for one of the Sewage Treatment Plant of Dravyavati River Rejuvenation Project in India and develops a Time Liner to identify logistics planning and clash detection. With this BIM processes, we shall find that there will be significant reduction of duplication of tasks and reworks. Also another benefit achieved will be better visualization and workarounds during conception stage and enables for early involvement of the stakeholders in the Project Life cycle of Sewage Treatment Plant construction. Moreover, we have also taken an opinion poll of the benefits accrued utilizing BIM processes versus traditional paper based communication like 2D and 3D CAD tools. Thus this paper concludes with BIM framework for Sewage Treatment Plant construction which will achieve optimal construction co-ordination advantages like 4D construction sequencing, interference checking, clash detection checking and resolutions by primary engagement of all key stakeholders thereby identifying potential risks and subsequent creation of risk response strategies. However, certain hiccups like hesitancy in adoption of BIM technology by naïve users and availability of proficient BIM trainers in India poses a phenomenal impediment. Hence the nurture of BIM processes from conception, construction and till commissioning, operation and maintenance along with deconstruction of a project’s life cycle is highly essential for Indian Construction Industry in this digital era.

Keywords: integrated BIM workflow, 4D planning with BIM, building information modeling, clash detection and visualization, constructability reviews, project life cycle

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Authors: Sonja Giese, Tess N. Peacock

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South African based Innovation Edge is experimenting with technology to drive positive behavior change, enable data-driven decision making, and scale quality early years services. This paper uses five case studies to illustrate how technology can be used in resource-constrained environments to first, encourage parenting practices that build early language development (using a stage-based mobile messaging pilot, ChildConnect), secondly, to improve the quality of ECD programs (using a mobile application, CareUp), thirdly, how to affordably scale services for the early detection of visual and hearing impairments (using a mobile tool, HearX), fourthly, how to build a transparent and accountable system for the registration and funding of ECD (using a blockchain enabled platform, Amply), and finally enable rapid data collection and feedback to facilitate quality enhancement of programs at scale (the Early Learning Outcomes Measure). ChildConnect and CareUp were both developed using a design based iterative research approach. The usage and uptake of ChildConnect and CareUp was evaluated with qualitative and quantitative methods. Actual child outcomes were not measured in the initial pilots. Although parents who used and engaged on either platform felt more supported and informed, parent engagement and usage remains a challenge. This is contrast to ECD practitioners whose usage and knowledge with CareUp showed both sustained engagement and knowledge improvement. HearX is an easy-to-use tool to identify hearing loss and visual impairment. The tool was tested with 10000 children in an informal settlement. The feasibility of cost-effectively decentralising screening services was demonstrated. Practical and financial barriers remain with respect to parental consent and for successful referrals. Amply uses mobile and blockchain technology to increase impact and accountability of public services. In the pilot project, Amply is being used to replace an existing paper-based system to register children for a government-funded pre-school subsidy in South Africa. Early Learning Outcomes Measure defines what it means for a child to be developmentally ‘on track’ at aged 50-69 months. ELOM administration is enabled via a tablet which allows for easy and accurate data collection, transfer, analysis, and feedback. ELOM is being used extensively to drive quality enhancement of ECD programs across multiple modalities. The nature of ECD services in South Africa is that they are in large part provided by disconnected private individuals or Non-Governmental Organizations (in contrast to basic education which is publicly provided by the government). It is a disparate sector which means that scaling successful interventions is that much harder. All five interventions show the potential of technology to support and enhance a range of ECD services, but pathways to scale are still being tested.

Keywords: assessment, behavior change, communication, data, disabilities, mobile, scale, technology, quality

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Authors: A. Sottomayor, M. Perez Duque, M. C. Henriques

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Introduction: Migration is not a new phenomenon; nomads often traveled, seeking better living conditions, including food and water. The increase of migrations affects all countries, rising health-related challenges. In Portugal, we have had migrant movements in the last decades, pairing with economic behavior. Irregular immigrants are detained in Santo António detention center from Portuguese Immigration and Borders Service (USHA-SEF) in Porto until court decision for a maximum of 60 days. It is the only long stay officially designated detention center for immigrants in Portugal. Immigrant health is important for public health (PH). It affects and is affected by the community. The XXVII Portuguese Government considered immigrant integration, including access to health, health promotion, protection and reduction of inequities a political priority. Many curative, psychological and legal services are provided for detainees, but until 2015, no structured health promotion or prevention actions were being held at USHA-SEF. That year, Porto Occidental PH Local Unit started to provide vaccination and health literacy on this theme for detainees and SEF workers. Our activities include a vaccine lecture, a medical consultation with vaccine prescription and administration, along with documented proof of vaccination. All vaccines are volunteer and free of charge. This action reduces the risk of importation and transmission of diseases, contributing to world eradication and elimination programs. We aimed to characterize the demography of irregular immigrant detained at UHSA-SEF and describe our activity. Methods: All data was provided by Porto Occidental Public Health Unit. All paper registers of vaccination were uploaded to MicrosoftExcel®. We included all registers and collected demographic variables, nationality, vaccination date, category, and administered vaccines. Descriptive analysis was performed using MicrosoftExcel®. Results: From 2015 to 2018, we delivered care to 256 individuals (179 immigrants; 77 workers). Considering immigrants, 72% were male, and 8 (16%) women were pregnant. 85% were between 20-54 years (ᵡ=30,8y; 2-71y), and 11 didn’t report any age. Migrants came from 48 countries, and India had the highest number (9%). MMR and Tetanus vaccines had > 90% vaccination rate and Poliomyelitis, hepatitis B and flu vaccines had around 85% vaccination rates. We had a consistent number of refusals. Conclusion: Our irregular migrant population comes from many different countries, which increases the risk of disease importation. Pregnant women are present as a particular subset of irregular migrants, and vaccination protects them and the baby. Vaccination of migrant is valuable for them and for the countries in which they pass. It contributes to universal health coverage, for eradication programmes and accomplishment of the Sustainable Development Goals. Peer influence may present as a determinant of refusals so we must consistently educate migrants before vaccination. More studies would be valuable, particularly on the migrant trajectory, duration of stay, destiny after court decision and health impact.

Keywords: migrants, public health, universal health coverage, vaccination

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Authors: Mona Isazad Mashinchi, Davood Roshan Sangachin, Francis J. Sullivan, Dietrich Rebholz-Schuhmann

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Background: Decision-making processes are nowadays driven by data, data analytics and Business Intelligence (BI). BI as a software platform can provide a wide variety of capabilities such as organization memory, information integration, insight creation and presentation capabilities. Visualizing data through dashboards is one of the BI solutions (for a variety of areas) which helps managers in the decision making processes to expose the most informative information at a glance. In the healthcare domain to date, dashboard presentations are more frequently used to track performance related metrics and less frequently used to monitor those quality parameters which relate directly to patient outcomes. Providing effective and timely care for patients and improving the health outcome are highly dependent on presenting and visualizing data and information. Objective: In this research, the focus is on the presentation capabilities of BI to design a dashboard for prostate cancer (PC) data that allows better decision making for the patients, the hospital and the healthcare system related to a cancer dataset. The aim of this research is to customize a retrospective PC dataset in a dashboard interface to give a better understanding of data in the categories (risk factors, treatment approaches, disease control and side effects) which matter most to patients as well as other stakeholders. By presenting the outcome in the dashboard we address one of the major targets of a value-based health care (VBHC) delivery model which is measuring the value and presenting the outcome to different actors in HC industry (such as patients and doctors) for a better decision making. Method: For visualizing the stored data to users, three interactive dashboards based on the PC dataset have been developed (using the Tableau Software) to provide better views to the risk factors, treatment approaches, and side effects. Results: Many benefits derived from interactive graphs and tables in dashboards which helped to easily visualize and see the patients at risk, better understanding the relationship between patient's status after treatment and their initial status before treatment, or to choose better decision about treatments with fewer side effects regarding patient status and etc. Conclusions: Building a well-designed and informative dashboard is related to three important factors including; the users, goals and the data types. Dashboard's hierarchies, drilling, and graphical features can guide doctors to better navigate through information. The features of the interactive PC dashboard not only let doctors ask specific questions and filter the results based on the key performance indicators (KPI) such as: Gleason Grade, Patient's Age and Status, but may also help patients to better understand different treatment outcomes, such as side effects during the time, and have an active role in their treatment decisions. Currently, we are extending the results to the real-time interactive dashboard that users (either patients and doctors) can easily explore the data by choosing preferred attribute and data to make better near real-time decisions.

Keywords: business intelligence, dashboard, decision making, healthcare, prostate cancer, value-based healthcare

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Authors: Muhammad Hanif Amiri, Edris Sadeqy, Ahmad Freed Osman

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International Conference on Architectural Engineering and Skyscraper (ICAES 2016) on January 18 - 19, 2016 is aimed to exchange new ideas and application experiences face to face, to establish business or research relations and to find global partners for future collaboration. Therefore, we are very keen to participate and share our issues in order to get valuable feedbacks of the conference participants. Urbanization is a controversial issue all around the world. Substandard and unplanned urbanization has many implications on a social, cultural and economic situation of population life. Unplanned and illegal construction has become a critical issue in Afghanistan particularly Kabul city. In addition, lack of municipal bylaws, poor municipal governance, lack of development policies and strategies, budget limitation, low professional capacity of ainvolved private sector in development and poor coordination among stakeholders are the other factors which made the problem more complicated. The main purpose of this research paper is to review urbanization pattern of Kabul city and find out the improvement solutions and to evaluate the increasing of population density which caused vast illegal and unplanned development which finally converts the Kabul city to a slam area as the whole. The Kabul city Master Plan was reviewed in the year 1978 and revised for the planned 2million population. In 2001, the interim administration took place and the city became influx of returnees from neighbor countries and other provinces of Afghanistan mostly for the purpose of employment opportunities, security and better quality of life, therefore, Kabul faced with strange population growth. According to Central Statistics Organization of Afghanistan population of Kabul has been estimated approx. 5 million (2015), however a new Master Plan has been prepared in 2009, but the existing challenges have not been dissolved yet. On the other hand, 70% of Kabul population is living in unplanned (slam) area and facing the shortage of drinking water, inexistence of sewerage and drainage network, inexistence of proper management system for solid waste collection, lack of public transportation and traffic management, environmental degradation and the shortage of social infrastructure. Although there are many problems in Kabul city, but still the development of 22 townships are in progress which caused the great attraction of population. The research is completed with a detailed analysis on four main issues such as elimination of duplicated administrations, Development of regions, Rehabilitation and improvement of infrastructure, and prevention of new townships establishment in Kabul Central Core in order to mitigate the problems and constraints which are the foundation and principal to find the point of departure for an objective based future development of Kabul city. The closure has been defined to reflect the stage-wise development in light of prepared policy and strategies, development of a procedure for the improvement of infrastructure, conducting a preliminary EIA, defining scope of stakeholder’s contribution and preparation of project list for initial development. In conclusion this paper will help the transformation of Kabul city.

Keywords: development of regions, illegal construction, population density, urbanization pattern

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Authors: Dace Grauda, Inta Belogrudova, Alexei Katashev, Linda Lancere, Isaak Rashal

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The goal of study was the elaboration of easy applicable flow cytometry method for detection of influence of abiotic stress factors on plants, which could be useful for detection of environmental stresses in urban areas. The lime tree Tillia vulgaris H. is a popular tree species used for urban landscaping in Europe and is one of the main species of street greenery in Riga, Latvia. Tree decline and low vitality has observed in the central part of Riga. For this reason lime trees were select as a model object for the investigation. During the period of end of June and beginning of July 12 samples from different urban environment locations as well as plant material from a greenhouse were collected. BD FACSJazz® cell sorter (BD Biosciences, USA) with flow cytometer function was used to test viability of plant cells. The method was based on changes of relative fluorescence intensity of cells in blue laser (488 nm) after influence of stress factors. SpheroTM rainbow calibration particles (3.0–3.4 μm, BD Biosciences, USA) in phosphate buffered saline (PBS) were used for calibration of flow cytometer. BD PharmingenTM PBS (BD Biosciences, USA) was used for flow cytometry assays. The mean fluorescence intensity information from the purified cell suspension samples was recorded. Preliminary, multiple gate sizes and shapes were tested to find one with the lowest CV. It was found that low CV can be obtained if only the densest part of plant cells forward scatter/side scatter profile is analysed because in this case plant cells are most similar in size and shape. The young pollen cells in one nucleus stage were found as the best for detection of influence of abiotic stress. For experiments only fresh plant material was used– the buds of Tillia vulgaris with diameter 2 mm. For the cell suspension (in vitro culture) establishment modified protocol of microspore culture was applied. The cells were suspended in the MS (Murashige and Skoog) medium. For imitation of dust of urban area SiO2 nanoparticles with concentration 0.001 g/ml were dissolved in distilled water. Into 10 ml of cell suspension 1 ml of SiO2 nanoparticles suspension was added, then cells were incubated in speed shaking regime for 1 and 3 hours. As a stress factor the irradiation of cells for 20 min by UV was used (Hamamatsu light source L9566-02A, L10852 lamp, A10014-50-0110), maximum relative intensity (100%) at 365 nm and at ~310 nm (75%). Before UV irradiation the suspension of cells were placed onto a thin layer on a filter paper disk (diameter 45 mm) in a Petri dish with solid MS media. Cells without treatment were used as a control. Experiments were performed at room temperature (23-25 °C). Using flow cytometer BS FACS Software cells plot was created to determine the densest part, which was later gated using oval-shaped gate. Gate included from 95 to 99% of all cells. To determine relative fluorescence of cells logarithmic fluorescence scale in arbitrary fluorescence units were used. 3x103 gated cells were analysed from the each sample. The significant differences were found among relative fluorescence of cells from different trees after treatment with SiO2 nanoparticles and UV irradiation in comparison with the control.

Keywords: flow cytometry, fluorescence, SiO2 nanoparticles, UV irradiation

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Authors: Vrushali Guhe, Shailza Singh

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

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

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Authors: Xiaoqing Peng, Aijing Luo, Yang Chen

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Background: Cyberchondria, as an "emerging risk" accompanied by the information era, is a new abnormal pattern characterized by excessive or repeated online searches for health-related information and escalating health anxiety, which endangers people's physical and mental health and poses a huge threat to public health. Objective: To explore and discuss the research status, hotspots and trends of Cyberchondria. Methods: Based on a total of 77 articles regarding "Cyberchondria" extracted from Web of Science from the beginning till October 2019, the literature trends, countries, institutions, hotspots are analyzed by bibliometric analysis, the concept definition of Cyberchondria, instruments, relevant factors, treatment and intervention are discussed as well. Results: Since "Cyberchondria" was put forward for the first time in 2001, the last two decades witnessed a noticeable increase in the amount of literature, especially during 2014-2019, it quadrupled dramatically at 62 compared with that before 2014 only at 15, which shows that Cyberchondria has become a new theme and hot topic in recent years. The United States was the most active contributor with the largest publication (23), followed by England (11) and Australia (11), while the leading institutions were Baylor University(7) and University of Sydney(7), followed by Florida State University(4) and University of Manchester(4). The WoS categories "Psychiatry/Psychology " and "Computer/ Information Science "were the areas of greatest influence. The concept definition of Cyberchondria is not completely unified in the world, but it is generally considered as an abnormal behavioral pattern and emotional state and has been invoked to refer to the anxiety-amplifying effects of online health-related searches. The first and the most frequently cited scale for measuring the severity of Cyberchondria called “The Cyberchondria Severity Scale (CSS) ”was developed in 2014, which conceptualized Cyberchondria as a multidimensional construct consisting of compulsion, distress, excessiveness, reassurance, and mistrust of medical professionals which was proved to be not necessary for this construct later. Since then, the Brazilian, German, Turkish, Polish and Chinese versions were subsequently developed, improved and culturally adjusted, while CSS was optimized to a simplified version (CSS-12) in 2019, all of which should be worthy of further verification. The hotspots of Cyberchondria mainly focuses on relevant factors as follows: intolerance of uncertainty, anxiety sensitivity, obsessive-compulsive disorder, internet addition, abnormal illness behavior, Whiteley index, problematic internet use, trying to make clear the role played by “associated factors” and “anxiety-amplifying factors” in the development of Cyberchondria, to better understand the aetiological links and pathways in the relationships between hypochondriasis, health anxiety and online health-related searches. Although the treatment and intervention of Cyberchondria are still in the initial stage of exploration, there are kinds of meaningful attempts to seek effective strategies from different aspects such as online psychological treatment, network technology management, health information literacy improvement and public health service. Conclusion: Research on Cyberchondria is in its infancy but should be deserved more attention. A conceptual consensus on Cyberchondria, a refined assessment tool, prospective studies conducted in various populations, targeted treatments for it would be the main research direction in the near future.

Keywords: cyberchondria, hypochondriasis, health anxiety, online health-related searches

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