Search results for: genetic variations

Authors: Layla Haidar, Shari Esquenazi-Karonika

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Introduction: Mental health includes one’s emotional, psychological, and interpersonal well-being; it ranges from “good” to “poor” on a continuum. At the individual-level, it affects how a person thinks, feels, and acts. Moreover, it determines how they cope with stress, relate to others, and interface with their surroundings. Research has yielded that mental health is directly related with short- and long-term physical health (including chronic disease), health risk behaviors, education-level, employment, and social relationships. As is the case with physical conditions like diabetes, heart disease, and cancer, mitigating the behavioral and genetic risks of debilitating mental health conditions like anxiety and depression can nurture a healthier quality of mental health throughout one’s life. In order to maximize the benefits of prevention, it is important to identify modifiable risks and develop protective habits earlier in life. Methods: The Adolescent Behaviors and Experiences Survey (ABES) dataset was used for this study. The ABES survey was administered to high school students (9th-12th grade) during January 2021- June 2021 by the Centers for Disease Control and Prevention (CDC). The data was analyzed to identify any associations between feelings of sadness, hopelessness, or increased suicidality among high school students with relation to their participation on one or more sports teams and their average daily consumed screen time. Data was analyzed using descriptive and multivariable analytic techniques. A multinomial logistic regression of each variable was conducted to examine if there was an association, while controlling for grade-level, sex, and race. Results: The findings from this study are insightful for administrators and policymakers who wish to address mounting concerns related to student mental health. The study revealed that compared to a student who participated on zero sports teams, students who participated in 1 or more sports teams showed a significantly increased risk of depression (p<0.05). Conversely, the rate of depression in students was significantly less in those who consumed 5 or more hours of screen time per day, compared to those who consumed less than 1 hour per day of screen time (p<0.05). Conclusion: These findings are informative and highlight the importance of understanding the nuances of student participation on sports teams (e.g., physical exertion, social dynamics of team, and the level of competitiveness within the sport). Likewise, the context of an individual’s screen time (e.g., social media, engaging in team-based video games, or watching television) can inform parental or school-based policies about screen time activity. Although physical activity has been proven to be important for emotional and physical well-being of youth, playing on multiple teams could have negative consequences on the emotional state of high school students potentially due to fatigue, overtraining, and injuries. Existing literature has highlighted the negative effects of screen time; however, further research needs to consider the type of screen-based consumption to better understand its effects on mental health.

Keywords: behavioral science, mental health, adolescents, prevention

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Authors: Olga V. Chervyakova, Elmira T. Tailakova, Vitaliy M. Strochkov, Kulyaisan T. Sultankulova, Nurlan T. Sandybayev, Lev G. Nemchinov, Rosemarie W. Hammond

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Sheep pox is a highly contagious infection that OIE regards to be one of the most dangerous animal diseases. It causes enormous economic losses because of death and slaughter of infected animals, lower productivity, cost of veterinary and sanitary as well as quarantine measures. To control spread of sheep pox infection the attenuated vaccines are widely used in the Republic of Kazakhstan and other Former Soviet Union countries. In spite of high efficiency of live vaccines, the possible presence of the residual virulence, potential genetic instability restricts their use in disease-free areas that leads to necessity to exploit new approaches in vaccine development involving recombinant DNA technology. Vaccines on the basis of recombinant proteins are the newest generation of prophylactic preparations. The main advantage of these vaccines is their low reactogenicity and this fact makes them widely used in medical and veterinary practice for vaccination of humans and farm animals. The objective of the study is to produce recombinant immunogenic proteins for development of the high-performance means for sheep pox prophylaxis. The SPV proteins were chosen for their homology with the known immunogenic vaccinia virus proteins. Assay of nucleotide and amino acid sequences of the target SPV protein genes. It has been shown that four proteins SPPV060 (ortholog L1), SPPV074 (ortholog H3), SPPV122 (ortholog A33) and SPPV141 (ortholog B5) possess transmembrane domains at N- or C-terminus while in amino acid sequences of SPPV095 (ortholog А 4) and SPPV117 (ortholog А 27) proteins these domains were absent. On the basis of these findings the primers were constructed. Target genes were amplified and subsequently cloned into the expression vector рЕТ26b(+) or рЕТ28b(+). Six constructions (pSPPV060ΔТМ, pSPPV074ΔТМ, pSPPV095, pSPPV117, pSPPV122ΔТМ and pSPPV141ΔТМ) were obtained for expression of the SPV genes under control of T7 promoter in Escherichia coli. To purify and detect recombinant proteins the amino acid sequences were modified by adding six histidine molecules at C-terminus. Induction of gene expression by IPTG was resulted in production of the proteins with molecular weights corresponding to the estimated values for SPPV060, SPPV074, SPPV095, SPPV117, SPPV122 and SPPV141, i.e. 22, 30, 20, 19, 17 and 22 kDa respectively. Optimal protocol of expression for each gene that ensures high yield of the recombinant protein was identified. Assay of cellular lysates by western blotting confirmed expression of the target proteins. Recombinant proteins bind specifically with antibodies to polyhistidine. Moreover all produced proteins are specifically recognized by the serum from experimentally SPV-infected sheep. The recombinant proteins SPPV060, SPPV074, SPPV117, SPPV122 and SPPV141 were also shown to induce formation of antibodies with virus-neutralizing activity. The results of the research will help to develop a new-generation high-performance means for specific sheep pox prophylaxis that is one of key moments in animal health protection. The research was conducted under the International project ISTC # K-1704 “Development of methods to construct recombinant prophylactic means for sheep pox with use of transgenic plants” and under the Grant Project RK MES G.2015/0115RK01983 "Recombinant vaccine for sheep pox prophylaxis".

Keywords: prophylactic preparation, recombinant protein, sheep pox virus, subunit vaccine

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Authors: Kaaryn Cater

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People vary in how they perceive, process, and react to internal, external, social, and emotional environmental factors; some are more sensitive than others. Compassionate people have a highly reactive nervous system and are more impacted by positive and negative environmental conditions (Differential Susceptibility). Further, some sensitive individuals are disproportionately able to benefit from positive and supportive environments without necessarily suffering negative impacts in less supportive environments (Vantage Sensitivity). Environmental sensitivity is underpinned by physiological, genetic, and personality/temperamental factors, and the phenotypic expression of high sensitivity is Sensory Processing Sensitivity. The hallmarks of Sensory Processing Sensitivity are deep cognitive processing, emotional reactivity, high levels of empathy, noticing environmental subtleties, a tendency to observe new and novel situations, and a propensity to become overwhelmed when over-stimulated. Several educational advantages associated with high sensitivity include creativity, enhanced memory, divergent thinking, giftedness, and metacognitive monitoring. High sensitivity can also lead to some educational challenges, particularly managing multiple conflicting demands and negotiating low sensory thresholds. A mixed methods study was undertaken. In the first quantitative study, participants completed the Perceived Success in Study Survey (PSISS) and the Highly Sensitive Person Scale (HSPS-12). Inclusion criteria were current or previous postsecondary education experience. The survey was presented on social media, and snowball recruitment was employed (n=365). The Excel spreadsheets were uploaded to the statistical package for the social sciences (SPSS)26, and descriptive statistics found normal distribution. T-tests and analysis of variance (ANOVA) calculations found no difference in the responses of demographic groups, and Principal Components Analysis and the posthoc Tukey calculations identified positive associations between high sensitivity and three of the five PSISS factors. Further ANOVA calculations found positive associations between the PSISS and two of the three sensitivity subscales. This study included a response field to register interest in further research. Respondents who scored in the 70th percentile on the HSPS-12 were invited to participate in a semi-structured interview. Thirteen interviews were conducted remotely (12 female). Reflexive inductive thematic analysis was employed to analyse data, and a descriptive approach was employed to present data reflective of participant experience. The results of this study found that compassionate students prioritize work-life balance; employ a range of practical metacognitive study and self-care strategies; value independent learning; connect with learning that is meaningful; and are bothered by aspects of the physical learning environment, including lighting, noise, and indoor environmental pollutants. There is a dearth of research investigating sensitivity in the educational context, and these studies highlight the need to promote widespread education sector awareness of environmental sensitivity, and the need to include sensitivity in sector and institutional diversity and inclusion initiatives.

Keywords: differential susceptibility, highly sensitive person, learning, neurosensitivity, sensory processing sensitivity, vantage sensitivity

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Authors: Shagufta Jabeen, Faez J. Firdaus Abdullah, Zunita Zakaria, Nurulfiza M. Isa, Yung C. Tan, Wai Y. Yee, Abdul R. Omar

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Pasteurella multocida (PM) is an important veterinary opportunistic pathogen particularly associated with septicemic pasteurellosis, pneumonic pasteurellosis and hemorrhagic septicemia in cattle and buffaloes. P. multocida serotype A has been reported to cause fatal pneumonia and septicemia. Pasteurella multocida subspecies multocida of serotype A Malaysian isolate PMTB2.1 was first isolated from buffaloes died of septicemia. In this study, the genome of P. multocida strain PMTB2.1 was sequenced using third-generation sequencing technology, PacBio RS2 system and analyzed bioinformatically via de novo analysis followed by in-depth analysis based on comparative genomics. Bioinformatics analysis based on de novo assembly of PacBio raw reads generated 3 contigs followed by gap filling of aligned contigs with PCR sequencing, generated a single contiguous circular chromosome with a genomic size of 2,315,138 bp and a GC content of approximately 40.32% (Accession number CP007205). The PMTB2.1 genome comprised of 2,176 protein-coding sequences, 6 rRNA operons and 56 tRNA and 4 ncRNAs sequences. The comparative genome sequence analysis of PMTB2.1 with nine complete genomes which include Actinobacillus pleuropneumoniae, Haemophilus parasuis, Escherichia coli and five P. multocida complete genome sequences including, PM70, PM36950, PMHN06, PM3480, PMHB01 and PMTB2.1 was carried out based on OrthoMCL analysis and Venn diagram. The analysis showed that 282 CDs (13%) are unique to PMTB2.1and 1,125 CDs with orthologs in all. This reflects overall close relationship of these bacteria and supports the classification in the Gamma subdivision of the Proteobacteria. In addition, genomic distance analysis among all nine genomes indicated that PMTB2.1 is closely related with other five Pasteurella species with genomic distance less than 0.13. Synteny analysis shows subtle differences in genetic structures among different P.multocida indicating the dynamics of frequent gene transfer events among different P. multocida strains. However, PM3480 and PM70 exhibited exceptionally large structural variation since they were swine and chicken isolates. Furthermore, genomic structure of PMTB2.1 is more resembling that of PM36950 with a genomic size difference of approximately 34,380 kb (smaller than PM36950) and strain-specific Integrative and Conjugative Elements (ICE) which was found only in PM36950 is absent in PMTB2.1. Meanwhile, two intact prophages sequences of approximately 62 kb were found to be present only in PMTB2.1. One of phage is similar to transposable phage SfMu. The phylogenomic tree was constructed and rooted with E. coli, A. pleuropneumoniae and H. parasuis based on OrthoMCL analysis. The genomes of P. multocida strain PMTB2.1 were clustered with bovine isolates of P. multocida strain PM36950 and PMHB01 and were separated from avian isolate PM70 and swine isolates PM3480 and PMHN06 and are distant from Actinobacillus and Haemophilus. Previous studies based on Single Nucleotide Polymorphism (SNPs) and Multilocus Sequence Typing (MLST) unable to show a clear phylogenetic relatedness between Pasteurella multocida and the different host. In conclusion, this study has provided insight on the genomic structure of PMTB2.1 in terms of potential genes that can function as virulence factors for future study in elucidating the mechanisms behind the ability of the bacteria in causing diseases in susceptible animals.

Keywords: comparative genomics, DNA sequencing, phage, phylogenomics

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Authors: Dionyssia Lyra, Shoaib Ismail

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Salinization of natural resources constitutes a significant component of the degradation force that leads to depletion of productive lands and fresh water reserves. The global extent of salt-affected soils is approximately 7% of the earth’s land surface and is expanding. The problems of excessive salt accumulation are most widespread in coastal, arid and semi-arid regions, where agricultural production is substantially hindered. The use of crops that can withstand high saline conditions is extremely interesting in such a context. Salt-loving plants or else ‘halophytes’ thrive when grown in hostile saline conditions, where traditional crops cannot survive. Salicornia bigelovii, a halophytic crop with multiple uses (vegetable, forage, biofuel), has demonstrated remarkable adaptability to harsh climatic conditions prevailing in dry areas with great potential for its expansion. Since 2011, the International Center for Biosaline Agriculture (ICBA) with Masdar Institute (MI) and King Abdul Aziz University of Science & Technology (KAUST) to look into the potential for growing S. bigelovii under hot and dry conditions. Through the projects undertaken, 50 different S. bigelovii genotypes were assessed under high saline conditions. The overall goal was to select the best performing S. bigelovii populations in terms of seed and biomass production for future breeding. Specific objectives included: 1) evaluation of selected S. bigelovii genotypes for various agronomic and growth parameters under field conditions, 2) seed multiplication of S. bigelovii using saline groundwater and 3) acquisition of inbred lines for further breeding. Field trials were conducted for four consecutive years at ICBA headquarters. During the first year, one Salicornia population was evaluated for seed and biomass production at different salinity levels, fertilizer treatments and planting methods. All growth parameters and biomass productivity for the salicornia population showed better performance with optimal biomass production in terms of both salinity level and fertilizer application. During the second year, 46 Salicornia populations (obtained from KAUST and Masdar Institute) were evaluated for 24 growth parameters and treated with groundwater through drip irrigation. The plant material originated from wild collections. Six populations were also assessed for their growth performance under full-strength seawater. Salicornia populations were highly variable for all characteristics under study for both irrigation treatments, indicating that there is a large pool of genetic information available for breeding. Irrigation with the highest level of salinity had a negative impact on the agronomic performance. The maximum seed yield obtained was 2 t/ha at 20 dS/m (groundwater treatment) at 25 cm x 25 cm planting distance. The best performing Salicornia populations for fresh biomass and seed yield were selected for the following season. After continuous selection, the best performing salicornia will be adopted for scaling-up options. Taking into account the results of the production field trials, salicornia expansion will be targeted in coastal areas of the Arabian Peninsula. As a crop with high biofuel and forage potential, its cultivation can improve the livelihood of local farmers.

Keywords: biosaline agriculture, genotypes selection, halophytes, Salicornia bigelovii

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Authors: Ron Dick, P. S. D. V. Prasadarao, Glenn Coltman

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Agenesis of the corpus callosum (ACC) is a failure to develop corpus callosum - the large bundle of fibers of the brain that connects the two cerebral hemispheres. It can occur as a partial or complete absence of the corpus callosum. In the general population, its estimated prevalence rate is 1 in 4000 and a wide range of genetic, infectious, vascular, and toxic causes have been attributed to this heterogeneous condition. The diagnosis of ACC is often achieved by neuroimaging procedures. Though persons with ACC can perform normally on intelligence tests they generally present with a range of neuropsychological and social deficits. The deficit profile is characterized by poor coordination of motor movements, slow reaction time, processing speed and, poor memory. Socially, they present with deficits in communication, language processing, the theory of mind, and interpersonal relationships. The present paper illustrates the role of neuropsychological assessment with implications to psychosocial management in a case of agenesis of the corpus callosum. Method: A 27-year old left handed Caucasian male with a history of ACC was self-referred for a neuropsychological assessment to assist him in his employment options. Parents noted significant difficulties with coordination and balance at an early age of 2-3 years and he was diagnosed with dyspraxia at the age of 14 years. History also indicated visual impairment, hypotonia, poor muscle coordination, and delayed development of motor milestones. MRI scan indicated agenesis of the corpus callosum with ventricular morphology, widely spaced parallel lateral ventricles and mild dilatation of the posterior horns; it also showed colpocephaly—a disproportionate enlargement of the occipital horns of the lateral ventricles which might be affecting his motor abilities and visual defects. The MRI scan ruled out other structural abnormalities or neonatal brain injury. At the time of assessment, the subject presented with such problems as poor coordination, slowed processing speed, poor organizational skills and time management, and difficulty with social cues and facial expressions. A comprehensive neuropsychological assessment was planned and conducted to assist in identifying the current neuropsychological profile to facilitate the formulation of a psychosocial and occupational rehabilitation programme. Results: General intellectual functioning was within the average range and his performance on memory-related tasks was adequate. Significant visuospatial and visuoconstructional deficits were evident across tests; constructional difficulties were seen in tasks such as copying a complex figure, building a tower and manipulating blocks. Poor visual scanning ability and visual motor speed were evident. Socially, the subject reported heightened social anxiety, difficulty in responding to cues in the social environment, and difficulty in developing intimate relationships. Conclusion: Persons with ACC are known to present with specific cognitive deficits and problems in social situations. Findings from the current neuropsychological assessment indicated significant visuospatial difficulties, poor visual scanning and problems in social interactions. His general intellectual functioning was within the average range. Based on the findings from the comprehensive neuropsychological assessment, a structured psychosocial rehabilitation programme was developed and recommended.

Keywords: agenesis, callosum, corpus, neuropsychology, psychosocial, rehabilitation

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Authors: Yiqi Zhu, Jean Francois Trani, Rameez Ulhassan

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Extreme weather phenomena increased by 46% between 2007 and 2017 and have become more intense with the rise in global average temperatures. This increased intensity of climate variations often induces humanitarian crises and particularly affects vulnerable populations in low- and middle-income countries (LMICs). Expectant and lactating mothers are among the most vulnerable groups. Pakistan ranks 10th among the most affected countries by climate disasters. In 2022, monsoon floods submerged a third of the country, causing the loss of 1,500 lives. Approximately 650,000 expectant and lactating mothers faced systematic stress from climatic disasters. Our study used participatory methods to investigate the systematic impact of climatic disasters on maternal health. In March 2023, we conducted six Group Model Building (GMB) workshops with healthcare workers, fathers, and mothers separately in two of the most affected areas in Pakistan. This study was approved by the Islamic Relief Research Review Board. GMB workshops consist of three sessions. In the first session, participants discussed the factors that impact maternal health. After identifying the factors, they discussed the connections among them and explored the system structures that collectively impact maternal health. Based on the discussion, a causal loop diagram (CLD) was created. Finally, participants discussed action ideas that could improve the system to enhance maternal health. Based on our discussions and the causal loop diagram, we identified interconnected factors at the family, community, and policy levels. Mothers and children are directly impacted by three interrelated factors: food insecurity, unstable housing, and lack of income. These factors create a reinforcing cycle that negatively affects both mothers and newborns. After the flood, many mothers were unable to produce sufficient breastmilk due to their health status. Without breastmilk and sufficient food for complementary feeding, babies tend to get sick in damp and unhygienic environments resulting from temporary or unstable housing. When parents take care of sick children, they miss out on income-generating opportunities. At the community level, the lack of access to clean water and sanitation (WASH) and maternal healthcare further worsens the situation. Structural failures such as a lack of safety nets and programs associated with flood preparedness make families increasingly vulnerable with each disaster. Several families reported that they had not fully recovered from a flood that occurred ten years ago, and this latest disaster destroyed their lives again. Although over twenty non-profit organizations are working in these villages, few of them provide sustainable support. Therefore, participants called for systemic changes in response to the increasing frequency of climate disasters. The study reveals the systematic vulnerabilities of mothers and children after climatic disasters. The most vulnerable populations are often affected the most by climate change. Collaborative efforts are required to improve water and forest management, strengthen public infrastructure, increase access to WASH, and gradually build climate-resilient communities. Governments, non-governmental organizations, and the community should work together to develop and implement effective strategies to prevent, mitigate, and adapt to climate change and its impacts.

Keywords: climatic disasters, maternal health, Pakistan, systematic impact, flood, disaster relief.

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Authors: Irakli Gamkrelidze, David Shengelia, Giorgi Chichinadze, Tamara Tsutsunava, Giorgi Beridze, Tamara Tsamalashvili, Ketevan Tedliashvili, Irakli Javakhishvili

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The Caucasus is situated between the Eurasian and Africa-Arabian plates and represents a component of the Mediterranean (Alpine-Himalayan) collision belt. The Loki crystalline massif crops out within one of the terranes of the Caucasus – Baiburt-Sevanian terrane. By the end of 2018, a digital geological map (1:50 000) of the Loki massif was compiled. The presented map is of great importance for the region since there is no large-scale geological map which reflects the present standards of the geological study of the massif up to the last time. The existing State Geological Map of the Loki massif is very outdated. A new map drown by using GIS (Geographic Information System) technology is loaded with multi-informative details that include: specified contours of geological units and separate tectonic scales, key mineral assemblages and facies of metamorphism, temperature conditions of metamorphism, ages of metamorphism events and the massif rocks, genetic-geodynamic types of magmatic rocks. Explanatory note, attached to the map includes the large specter of scientific information. It contains characterization of the geological setting, composition and petrogenetic and geodynamic models of the massif formation. To create a geological map of the Loki crystalline massif, appropriate methodologies were applied: a sampling of rocks, GIS technology-based mapping of geological units, microscopic description of the material, composition analysis of rocks, microprobe analysis of minerals and a new interpretation of obtained data. To prepare a digital version of the map the appropriated activities were held including the creation of a common database. Finally, the design was created that includes the elaboration of legend and the final visualization of the map. The results of the study presented in the explanatory note are given below. The autochthonous gneissose quartz diorites of normal alkalinity and sub-alkaline gabbro-diorites included in them belong to different phases of magmatism. They represent “igneous” granites corresponding to mixed mantle-crustal type granites. Four tectonic plates of the allochthonous metamorphic complex–Lower Gorastskali, Sapharlo–Lok-Jandari, Moshevani, and Lower Gorastskali differ from each other by structure and degree of metamorphism. The initial rocks of these plates are formed in different geodynamic conditions and during the Early Bretonian orogeny while overthrusting due to tectonic compression they form a thick tectonic sheet. The Lower Gorastskali overthrust sheet is a fragment of ophiolitic association corresponding to the Paleotethys oceanic crust. The protolith of the ophiolitic complex basites corresponds to the tholeiitic series of basalts. The Sapharlo–Lok-Jandari overthrust sheet is metapelites, metamorphosed in conditions of greenschist facies of regional metamorphism. The regional metamorphism of Moshevani overthrust sheet crystalline schists quartzites corresponds to a range from greenschist to hornfels facies. The “mélange” is built of rock fragments and blocks of above-mentioned overthrust sheets. Sub-alkaline and normal alkaline post-metamorphic granites of the Loki crystalline massif belong to “igneous” and rarely to “sialic” and “anorogenic” types of granites.

Keywords: digital geological map, 1:50 000 scale, crystalline massif, the caucasus

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Authors: Aleksandra Chałupnik, Zuzanna Chilimoniuk, Joanna Borowik, Aleksandra Borkowska, Anna Torres

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Background: Precocious puberty is the occurrence of secondary sexual characteristics in girls before the age of 8. The diverse etiology of premature puberty is crucial to determine whether it is true precocious puberty, depending on the activation of the hypothalamic-pituitary-gonadal axis, or pseudo-precocious, which is independent of the activation of this axis. Whatever the cause, premature action of the sex hormones leads to the common symptoms of various forms of puberty. These include the development of sexual characteristics, acne, acceleration of growth rate and acceleration of skeletal maturation. Due to the possible genetic basis of the disorders, an interdisciplinary search for the cause is needed. Case report: The case report concerns a patient of a pediatric gynecology clinic who, at the age of two years, developed advanced thelarhe (M3) and started recurrent vaginal bleeding. In August 2019, gonadotropin suppression initially and after LHRH stimulation and high estradiol levels were reported at the Endocrinology Department. Imaging examinations showed a cyst in the right ovary projection. The bone age was six years. The entire clinical picture indicated pseudo- (peripheral) precocious in the course of ovarian autonomic cyst. In the follow-up ultrasound performed in September, the image of the cyst was stationary and normalization of estradiol levels and clinical symptoms was noted. In December 2019, cyst regression and normal gonadotropin and estradiol concentrations were found. In June 2020, white mucus tinged with blood on the underwear, without any other disturbing symptoms, was observed for several days. Two consecutive USG examinations carried out in the same month confirmed the change in the right ovary, the diameter of which was 25 mm with a very high level of estradiol. Germinal tumor markers were normal. On the Tanner scale, the patient scored M2P1. The labia and hymen had puberty features. The correct vaginal entrance was visible. Another active vaginal bleeding occurred in the first week of July 2020. The considered laparoscopic treatment was abandoned due to the lack of oncological indications. Treatment with Tamoxifen was recommended in July 2020. In the initiating period of treatment, no maturation progression, and even reduction of symptoms, no acceleration of growth and a marked reduction in the size of the cysts were noted. There was no bleeding. After the size of the cyst and hormonal activity increased again, the treatment was changed to Anastrozole, the effect of which led to a reduction in the size of the cyst. Conclusions: The entire clinical picture indicates alleged (peripheral) puberty. Premature puberty in girls, which is manifested as enlarged mammary glands with high levels of estrogens secreted by autonomic ovarian cysts and prepubertal levels of gonadotropins, may indicate McCune-Albright syndrome. Vaginal bleeding may also occur in this syndrome. Cancellation of surgical treatment of the cyst made it impossible to perform a molecular test that would allow to confirm the diagnosis. Taking into account the fact that cysts are often one of the first symptoms of McCune-Albrigt syndrome, it is important to remember about multidisciplinary care for the patient and careful search for skin and bone changes or other hormonal disorders.

Keywords: McCune Albrigth's syndrome, ovarian cyst, pediatric gynaecology, precocious puberty

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Authors: Kristina Karapetyan, Flora Tkhruni, Tsovinar Balabekyan, Arevik Israyelyan, Tatyana Khachatryan

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The ability of the lactic acid bacteria (LAB) to prevent and cure a variety of diseases, their protective role against infections and colonization of pathogenic microorganisms in the digestive tract, has lead to the coining of the term probiotics or pro-life. LAB inhibiting the growth of pathogenic and food spoilage microorganisms, maintaining the nutritive quality and improving the shelf life of foods. They have also been used as flavor and texture producers. Enterococcus strains have been used for treatment of diseases such as diarrhea or antibiotic associated diarrhea, inflammatory pathologies that affect colon such as irritable bowel syndrome, or immune regulation, diarrhea caused by antibiotic treatments. The obtaining and investigation of biological properties of proteinoceous antibiotics, on the basis of probiotic LAB shown, that bacteriocins, metabiotics, and peptides of LAB represent bactericides have a broad range of activity and are excellent candidates for development of new prophylactic and therapeutic substances to complement or replace conventional antibiotics. The genotyping by 16S rRNA sequencing for LAB were used. Cell free culture broth (CFC) broth was purified by the Gel filtration method on the Sephadex Superfine G 25 resin. Antimicrobial activity was determined by spot-on-lawn method and expressed in arbitrary units (AU/ml). The diversity of multidrug-resistance (MDR) of pathogenic strains to antibiotics, most widely used for treatment of human diseases in the Republics of Armenia and Nagorno Karabakh were examined. It was shown, that difference of resistance of pathogens to antibiotics depends on their isolation sources. The influences of partially purified antimicrobial preparations (AMP), obtained from the different strains of Enterococcus genus on the growth of MDR pathogenic bacteria were investigated. It was shown, that bacteriocin containing partially purified preparations, obtained from different strains of Enterococcus faecium and durans species, possess bactericidal or bacteriostatic activity against antibiotic resistant intestinal, spoilage and food-borne pathogens such as Listeria monocytogenes, Staphylococcus aureus, E. coli, and Salmonella. Endemic strains of LAB, isolated from Matsoni made from donkey, buffalo and goat milk, shown broad spectrum of activity against food spoiling microorganisms, moulds and fungi, such as Salmonella sp., Esherichia coli, Aspergillus and Penicillium species. Highest activity against MDR pathogens shown bacteria, isolated from goat milk products. High stability of the investigated strains of the genus Enerococcus, isolated from samples of matsun from different regions of Nagorno-Karabakh (NKR) to the antibiotics was shown. The obtained data show high stability of the investigated different strains of the genus Enerococcus. The high genetic diversity in Enterococcus group suggests adaptations for specific mutations in different environments. Thus, endemic strains of LAB are able to produce bacteriocins with high and different inhibitory activity against broad spectrum of microorganisms isolated from different sources and belong to different taxonomic group. Prospect of the use of certain antimicrobial preparations against pathogenic strains is obvious. These AMP can be applied for long term use against different etiology antibiotic resistant pathogens for prevention or treatment of infectional diseases as an alternative to antibiotics.

Keywords: antimicrobial biopreparation, endemic lactic acid bacteria, intra-species diversity, multidrug resistance of pathogens

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Authors: Todd H. Buxton, Yong G. Lai

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Temperature management in regulated rivers can involve significant expenditures of water to meet the cold-water requirements of species in summer. For this purpose, flows released from Lewiston Dam on the Trinity River in Northern California are 12.7 cms with temperatures around 11oC in July through September to provide adult spring Chinook cold water to hold in deep pools and mature until spawning in fall. The releases are more than double the flow and 10oC colder temperatures than the natural conditions before the dam was built. The high, cold releases provide springers the habitat they require but may suppress the stream food base and limit future populations of salmon by reducing the juvenile fish size and survival to adults via the positive relationship between the two. Field and modeling research was undertaken to explore whether lowering summer releases from Lewiston Dam may promote thermal stratification in river pools so that both the cold-water needs of adult salmon and warmer water requirements of other organisms in the stream biome may be met. For this investigation, a three-dimensional (3D) computational fluid dynamics (CFD) model was developed and validated with field measurements in two deep pools on the Trinity River. Modeling and field observations were then used to identify the flows and temperatures that may form and maintain thermal stratification under different meteorologic conditions. Under low flows, a pool was found to be well mixed and thermally homogenous until temperatures began to stratify shortly after sunrise. Stratification then strengthened through the day until shading from trees and mountains cooled the inlet flow and decayed the thermal gradient, which collapsed shortly before sunset and returned the pool to a well-mixed state. This diurnal process of stratification formation and destruction was closely predicted by the 3D CFD model. Both the model and field observations indicate that thermal stratification maintained the coldest temperatures of the day at ≥2m depth in a pool and provided water that was around 8oC warmer in the upper 2m of the pool. Results further indicate that the stratified pool under low flows provided almost the same daily average temperatures as when flows were an order of magnitude higher and stratification was prevented, indicating significant water savings may be realized in regulated streams while also providing a diversity in water temperatures the ecosystem requires. With confidence in the 3D CFD model, the model is now being applied to a dozen pools in the Trinity River to understand how pool bathymetry influences thermal stratification under variable flows and diurnal temperature variations. This knowledge will be used to expand the results to 52 pools in a 64 km reach below Lewiston Dam that meet the depth criteria (≥2 m) for spring Chinook holding. From this, rating curves will be developed to relate discharge to the volume of pool habitat that provides springers the temperature (<15.6oC daily average), velocity (0.15 to 0.4 m/s) and depths that accommodate the escapement target for spring Chinook (6,000 adults) under maximum fish densities measured in other streams (3.1 m3/fish) during the holding time of year (May through August). Flow releases that meet these goals will be evaluated for water savings relative to the current flow regime and their influence on indicator species, including the Foothill Yellow-Legged Frog, and aspects of the stream biome that support salmon populations, including macroinvertebrate production and juvenile Chinook growth rates.

Keywords: 3D CFD modeling, flow regulation, thermal stratification, chinook salmon, foothill yellow-legged frogs, water managment

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Authors: Salam N. Abdo, Orien L. Tulp, George P. Einstein

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The purpose of this exploratory study was to gather the insights into psoriasis etiology, treatment, and patient experience, for developing psoriasis and psoriatic arthritis diagnostic test. Data collection methods consisted of a comprehensive meta-analysis of relevant studies and psoriasis patient survey. Established meta-analysis guidelines were used for the selection and qualitative comparative analysis of psoriasis and psoriatic arthritis research studies. Only studies that clearly discussed psoriasis etiology, treatment, and patient experience were reviewed and analyzed, to establish a qualitative data base for the study. Using the insights gained from meta-analysis, an existing psoriasis patient survey was modified and administered to collect additional data as well as triangulate the results. The hypothesis is that specific types of psoriatic disease have specific etiology and pathophysiologic pattern. The following etiology categories were identified: bacterial, environmental/microbial, genetic, immune, infectious, trauma/stress, and viral. Additional results, obtained from meta-analysis and confirmed by patient survey, were the common age of onset (early to mid-20s) and type of psoriasis (plaque; mild; symmetrical; scalp, chest, and extremities, specifically elbows and knees). Almost 70% of patients reported no prescription drug use due to severe side effects and prohibitive cost. These results will guide the development of psoriasis and psoriatic arthritis diagnostic test. The significant number of medical publications classified psoriatic arthritis disease as inflammatory of an unknown etiology. Thus numerous meta-analyses struggle to report any meaningful conclusions since no definitive results have been reported to date. Therefore, return to the basics is an essential step to any future meaningful results. To date, medical literature supports the fact that psoriatic disease in its current classification could be misidentifying subcategories, which in turn hinders the success of studies conducted to date. Moreover, there has been an enormous commercial support to pursue various immune-modulation therapies, thus following a narrow hypothesis/mechanism of action that is yet to yield resolution of disease state. Recurrence and complications may be considered unacceptable in a significant number of these studies. The aim of the ongoing study is to focus on a narrow subgroup of patient population, as identified by this exploratory study via meta-analysis and patient survey, and conduct an exhaustive work up, aiming at mechanism of action and causality before proposing a cure or therapeutic modality. Remission in psoriasis has been achieved and documented in medical literature, such as immune-modulation, phototherapy, various over-the-counter agents, including salts and tar. However, there is no psoriasis and psoriatic arthritis diagnostic test to date, to guide the diagnosis and treatment of this debilitating and, thus far, incurable disease. Because psoriasis affects approximately 2% of population, the results of this study may affect the treatment and improve the quality of life of a significant number of psoriasis patients, potentially millions of patients in the United States alone and many more millions worldwide.

Keywords: biologics, early diagnosis, etiology, immune disease, immune modulation therapy, inflammation skin disorder, phototherapy, plaque psoriasis, psoriasis, psoriasis classification, psoriasis disease marker, psoriasis diagnostic test, psoriasis marker, psoriasis mechanism of action, psoriasis treatment, psoriatic arthritis, psoriatic disease, psoriatic disease marker, psoriatic patient experience, psoriatic patient quality of life, remission, salt therapy, targeted immune therapy

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Authors: C. Bel, J. Nevado, F. Ciceri, M. Ropacki, T. Hoffmann, P. Lapunzina, C. Buesa

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Background: The Phelan-McDermid syndrome (PMS) is a genetic disorder caused by the deletion of the terminal region of chromosome 22 or mutation of the SHANK3 gene. Shank3 disruption in mice leads to dysfunction of synaptic transmission, which can be restored by epigenetic regulation with both Lysine Specific Demethylase 1 (LSD1) inhibitors. PMS subjects result in a variable degree of intellectual disability, delay or absence of speech, autistic spectrum disorders symptoms, low muscle tone, motor delays and epilepsy. Vafidemstat is an LSD1 inhibitor in Phase II clinical development with a well-established and favorable safety profile, and data supporting the restoration of memory and cognition defects as well as reduction of agitation and aggression in several animal models and clinical studies. Therefore, vafidemstat has the potential to become a first-in-class precision medicine approach to treat PMS patients. Aims: The goal of this research is to perform an observational trial to psychometrically characterize individuals carrying deletions in SHANK3 and build a foundation for subsequent precision psychiatry clinical trials with vafidemstat. Methodology: This study is characterizing the clinical profile of 20 to 40 subjects, > 16-year-old, with genotypically confirmed PMS diagnosis. Subjects will complete a battery of neuropsychological scales, including the Repetitive Behavior Questionnaire (RBQ), Vineland Adaptive Behavior Scales, Escala de Observación para el Diagnostico del Autismo (Autism Diagnostic Observational Scale) (ADOS)-2, the Battelle Developmental Inventory and the Behavior Problems Inventory (BPI). Results: By March 2021, 19 patients have been enrolled. Unsupervised hierarchical clustering of the results obtained so far identifies 3 groups of patients, characterized by different profiles of cognitive and behavioral scores. The first cluster is characterized by low Battelle age, high ADOS and low Vineland, RBQ and BPI scores. Low Vineland, RBQ and BPI scores are also detected in the second cluster, which in contrast has high Battelle age and low ADOS scores. The third cluster is somewhat in the middle for the Battelle, Vineland and ADOS scores while displaying the highest levels of aggression (high BPI) and repeated behaviors (high RBQ). In line with the observation that female patients are generally affected by milder forms of autistic symptoms, no male patients are present in the second cluster. Dividing the results by gender highlights that male patients in the third cluster are characterized by a higher frequency of aggression, whereas female patients from the same cluster display a tendency toward higher repetitive behavior. Finally, statistically significant differences in deletion sizes are detected comparing the three clusters (also after correcting for gender), and deletion size appears to be positively correlated with ADOS and negatively correlated with Vineland A and C scores. No correlation is detected between deletion size and the BPI and RBQ scores. Conclusions: Precision medicine may open a new way to understand and treat Central Nervous System disorders. Epigenetic dysregulation has been proposed to be an important mechanism in the pathogenesis of schizophrenia and autism. Vafidemstat holds exciting therapeutic potential in PMS, and this study will provide data regarding the optimal endpoints for a future clinical study to explore vafidemstat ability to treat shank3-associated psychiatric disorders.

Keywords: autism, epigenetics, LSD1, personalized medicine

Procedia PDF Downloads 141

Authors: Georgina Cherry, Taranpreet Rai, Luke Boyden, Sitira Williams, Andrea Wright, Richard Brown, Viva Chu, Alasdair Cook, Kevin Wells

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Estimating population-level burden, abilities of pet-parents to identify disease and demand for veterinary services worldwide is challenging. The purpose of this study is to compare a feline pruritus survey with social media listening (SML) data discussing this condition. Surveys are expensive and labour intensive to analyse, but SML data is freeform and requires careful filtering for relevancy. This study considers data from a survey of owner-observed symptoms of 156 pruritic cats conducted using Pet Parade® and SML posts collected through web-scraping to gain insights into the characterisation and management of feline pruritus. SML posts meeting a feline body area, behaviour and symptom were captured and reviewed for relevance representing 1299 public posts collected from 2021 to 2023. The survey involved 1067 pet-parents who reported on pruritic symptoms in their cats. Among the observed cats, approximately 18.37% (n=196) exhibited at least one symptom. The most frequently reported symptoms were hair loss (9.2%), bald spots (7.3%) and infection, crusting, scaling, redness, scabbing, scaling, or bumpy skin (8.2%). Notably, bald spots were the primary symptom reported for short-haired cats, while other symptoms were more prevalent in medium and long-haired cats. Affected body areas, according to pet-parents, were primarily the head, face, chin, neck (27%), and the top of the body, along the spine (22%). 35% of all cats displayed excessive behaviours consistent with pruritic skin disease. Interestingly, 27% of these cats were perceived as non-symptomatic by their owners, suggesting an under-identification of itch-related signs. Furthermore, a significant proportion of symptomatic cats did not receive any skin disease medication, whether prescribed or over the counter (n=41). These findings indicate a higher incidence of pruritic skin disease in cats than recognized by pet owners, potentially leading to a lack of medical intervention for clinically symptomatic cases. The comparison between the survey and social media listening data revealed bald spots were reported in similar proportions in both datasets (25% in the survey and 28% in SML). Infection, crusting, scaling, redness, scabbing, scaling, or bumpy skin accounted for 31% of symptoms in the survey, whereas it represented 53% of relevant SML posts (excluding bumpy skin). Abnormal licking or chewing behaviours were mentioned by pet-parents in 40% of SML posts compared to 38% in the survey. The consistency in the findings of these two disparate data sources, including a complete overlap in affected body areas for the top 80% of social media listening posts, indicates minimal biases in each method, as significant biases would likely yield divergent results. Therefore, the strong agreement across pruritic symptoms, affected body areas, and reported behaviours enhances our confidence in the reliability of the findings. Moreover, the small differences identified between the datasets underscore the valuable insights that arise from utilising multiple data sources. These variations provide additional depth in characterising and managing feline pruritus, allowing for more comprehensive understanding of the condition. By combining survey data and social media listening, researchers can obtain a nuanced perspective and capture a wider range of experiences and perspectives, supporting informed decision-making in veterinary practice.

Keywords: social media listening, feline pruritus, surveys, felines, cats, pet owners

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Authors: Diogo José Morgado Rebelo, Francisco António Carneiro Pacheco de Andrade, Paulo Jorge Freitas de Oliveira Novais

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Not everything in AI-power consumer credit scoring turns out to be a wonder. When using AI in Creditworthiness Assessment (CWA), opacity and unfairness ‘sins’ must be considered to the task be deemed Responsible. AI software is not always 100% accurate, which can lead to misclassification. Discrimination of some groups can be exponentiated. A hetero personalized identity can be imposed on the individual(s) affected. Also, autonomous CWA sometimes lacks transparency when using black box models. However, for this intended purpose, human analysts ‘on-the-loop’ might not be the best remedy consumers are looking for in credit. This study seeks to explore the legality of implementing a Multi-Agent System (MAS) framework in consumer CWA to ensure compliance with the regulation outlined in Article 14(4) of the Proposal for an Artificial Intelligence Act (AIA), dated 21 April 2021 (as per the last corrigendum by the European Parliament on 19 April 2024), Especially with the adoption of Art. 18(8)(9) of the EU Directive 2023/2225, of 18 October, which will go into effect on 20 November 2026, there should be more emphasis on the need for hybrid oversight in AI-driven scoring to ensure fairness and transparency. In fact, the range of EU regulations on AI-based consumer credit will soon impact the AI lending industry locally and globally, as shown by the broad territorial scope of AIA’s Art. 2. Consequently, engineering the law of consumer’s CWA is imperative. Generally, the proposed MAS framework consists of several layers arranged in a specific sequence, as follows: firstly, the Data Layer gathers legitimate predictor sets from traditional sources; then, the Decision Support System Layer, whose Neural Network model is trained using k-fold Cross Validation, provides recommendations based on the feeder data; the eXplainability (XAI) multi-structure comprises Three-Step-Agents; and, lastly, the Oversight Layer has a 'Bottom Stop' for analysts to intervene in a timely manner. From the analysis, one can assure a vital component of this software is the XAY layer. It appears as a transparent curtain covering the AI’s decision-making process, enabling comprehension, reflection, and further feasible oversight. Local Interpretable Model-agnostic Explanations (LIME) might act as a pillar by offering counterfactual insights. SHapley Additive exPlanation (SHAP), another agent in the XAI layer, could address potential discrimination issues, identifying the contribution of each feature to the prediction. Alternatively, for thin or no file consumers, the Suggestion Agent can promote financial inclusion. It uses lawful alternative sources such as the share of wallet, among others, to search for more advantageous solutions to incomplete evaluation appraisals based on genetic programming. Overall, this research aspires to bring the concept of Machine-Centered Anthropocentrism to the table of EU policymaking. It acknowledges that, when put into service, credit analysts no longer exert full control over the data-driven entities programmers have given ‘birth’ to. With similar explanatory agents under supervision, AI itself can become self-accountable, prioritizing human concerns and values. AI decisions should not be vilified inherently. The issue lies in how they are integrated into decision-making and whether they align with non-discrimination principles and transparency rules.

Keywords: creditworthiness assessment, hybrid oversight, machine-centered anthropocentrism, EU policymaking

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Authors: Farid Risheq, M. Zaid Alrisheq, Shuaa Al-Sadoon, Karim Al-Faqih, Mays Abdulazeez

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Breast cancer is the most frequently diagnosed cancer worldwide, and a common cause of death among women. Various conventional anatomical imaging tools are utilized for diagnosis, histological assessment and TNM (Tumor, Node, Metastases) staging of breast cancer. Biopsy of sentinel lymph node is becoming an alternative to the axillary lymph node dissection. Advances in 18-Fluoro-Deoxi-Glucose Positron Emission Tomography/Computed Tomography (18FDG-PET/CT) imaging have facilitated breast cancer diagnosis utilizing biological trapping of 18FDG inside lesion cells, expressed as Standardized Uptake Value (SUVmax). Objective: To present the utility of 18FDG uptake PET/CT scans in detecting active extra lymph nodes and distant occult metastases for breast cancer staging. Subjects and Methods: Four female patients were presented with initially classified TNM stages of breast cancer based on conventional anatomical diagnostic techniques. 18FDG-PET/CT scans were performed one hour post 18FDG intra-venous injection of (300-370) MBq, and (7-8) bed/130sec. Transverse, sagittal, and coronal views; fused PET/CT and MIP modality were reconstructed for each patient. Results: A total of twenty four lesions in breast, extended lesions to lung, liver, bone and active extra lymph nodes were detected among patients. The initial TNM stage was significantly changed post 18FDG-PET/CT scan for each patient, as follows: Patient-1: Initial TNM-stage: T1N1M0-(stage I). Finding: Two lesions in right breast (3.2cm2, SUVmax=10.2), (1.8cm2, SUVmax=6.7), associated with metastases to two right axillary lymph nodes. Final TNM-stage: T1N2M0-(stage II). Patient-2: Initial TNM-stage: T2N2M0-(stage III). Finding: Right breast lesion (6.1cm2, SUVmax=15.2), associated with metastases to right internal mammary lymph node, two right axillary lymph nodes, and sclerotic lesions in right scapula. Final TNM-stage: T2N3M1-(stage IV). Patient-3: Initial TNM-stage: T2N0M1-(stage III). Finding: Left breast lesion (11.1cm2, SUVmax=18.8), associated with metastases to two lymph nodes in left hilum, and three lesions in both lungs. Final TNM-stage: T2N2M1-(stage IV). Patient-4: Initial TNM-stage: T4N1M1-(stage III). Finding: Four lesions in upper outer quadrant area of right breast (largest: 12.7cm2, SUVmax=18.6), in addition to one lesion in left breast (4.8cm2, SUVmax=7.1), associated with metastases to multiple lesions in liver (largest: 11.4cm2, SUV=8.0), and two bony-lytic lesions in left scapula and cervicle-1. No evidence of regional or distant lymph node involvement. Final TNM-stage: T4N0M2-(stage IV). Conclusions: Our results demonstrated that 18FDG-PET/CT scans had significantly changed the TNM stages of breast cancer patients. While the T factor was unchanged, N and M factors showed significant variations. A single session of PET/CT scan was effective in detecting active extra lymph nodes and distant occult metastases, which were not identified by conventional diagnostic techniques, and might advantageously replace bone scan, and contrast enhanced CT of chest, abdomen and pelvis. Applying 18FDG-PET/CT scan early in the investigation, might shorten diagnosis time, helps deciding adequate treatment protocol, and could improve patients’ quality of life and survival. Trapping of 18FDG in malignant lesion cells, after a PET/CT scan, increases the retention index (RI%) for a considerable time, which might help localize sentinel lymph node for biopsy using a hand held gamma probe detector. Future work is required to demonstrate its utility.

Keywords: axillary lymph nodes, breast cancer staging, fluorodeoxyglucose positron emission tomography/computed tomography, lymph nodes

Procedia PDF Downloads 285

Authors: Manon Frédout, Laëtitia Bucari, Mathias Aloui, Gaëtan Duhamel, Olivier Rovellotti, Javier Blanco

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Ecosystems must be resilient to ensure cleaner air, better water and soil quality, and thus healthier citizens. Technology can be an excellent tool to support urban ecosystem restoration projects, especially when based on Open Source and promoting Open Data. This is the goal of the ecoTeka application: one single digital tool for tree management which allows decision-makers to improve their urban forestry practices, enabling more responsible urban planning and climate change adaptation. EcoTeka provides city councils with three main functionalities tackling three of their challenges: easier biodiversity inventories, better green space management, and more efficient planning. To answer the cities’ need for reliable tree inventories, the application has been first built with open data coming from the websites OpenStreetMap and OpenTrees, but it will also include very soon the possibility of creating new data. To achieve this, a multi-source algorithm will be elaborated, based on existing artificial intelligence Deep Forest, integrating open-source satellite images, 3D representations from LiDAR, and street views from Mapillary. This data processing will permit identifying individual trees' position, height, crown diameter, and taxonomic genus. To support urban forestry management, ecoTeka offers a dashboard for monitoring the city’s tree inventory and trigger alerts to inform about upcoming due interventions. This tool was co-constructed with the green space departments of the French cities of Alès, Marseille, and Rouen. The third functionality of the application is a decision-making tool for urban planning, promoting biodiversity and landscape connectivity metrics to drive ecosystem restoration roadmap. Based on landscape graph theory, we are currently experimenting with new methodological approaches to scale down regional ecological connectivity principles to local biodiversity conservation and urban planning policies. This methodological framework will couple graph theoretic approach and biological data, mainly biodiversity occurrences (presence/absence) data available on both international (e.g., GBIF), national (e.g., Système d’Information Nature et Paysage) and local (e.g., Atlas de la Biodiversté Communale) biodiversity data sharing platforms in order to help reasoning new decisions for ecological networks conservation and restoration in urban areas. An experiment on this subject is currently ongoing with Montpellier Mediterranee Metropole. These projects and studies have shown that only 26% of tree inventory data is currently geo-localized in France - the rest is still being done on paper or Excel sheets. It seems that technology is not yet used enough to enrich the knowledge city councils have about biodiversity in their city and that existing biodiversity open data (e.g., occurrences, telemetry, or genetic data), species distribution models, landscape graph connectivity metrics are still underexploited to make rational decisions for landscape and urban planning projects. This is the goal of ecoTeka: to support easier inventories of urban biodiversity and better management of urban spaces through rational planning and decisions relying on open databases. Future studies and projects will focus on the development of tools for reducing the artificialization of soils, selecting plant species adapted to climate change, and highlighting the need for ecosystem and biodiversity services in cities.

Keywords: digital software, ecological design of urban landscapes, sustainable urban development, urban ecological corridor, urban forestry, urban planning

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Authors: Nayer Mofidtabatabaei

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Advancements in artificial intelligence (AI) have transformed various fields, including psychology and behavioral sciences. This paper explores the diverse ways in which AI is applied to enhance research, diagnosis, therapy, and understanding of human behavior and mental health. We discuss the potential benefits and challenges associated with AI in these fields, emphasizing the ethical considerations and the need for collaboration between AI researchers and psychological and behavioral science experts. Artificial Intelligence (AI) has gained prominence in recent years, revolutionizing multiple industries, including healthcare, finance, and entertainment. One area where AI holds significant promise is the field of psychology and behavioral sciences. AI applications in this domain range from improving the accuracy of diagnosis and treatment to understanding complex human behavior patterns. This paper aims to provide an overview of the various AI applications in psychological and behavioral sciences, highlighting their potential impact, challenges, and ethical considerations. Mental Health Diagnosis AI-driven tools, such as natural language processing and sentiment analysis, can analyze large datasets of text and speech to detect signs of mental health issues. For example, chatbots and virtual therapists can provide initial assessments and support to individuals suffering from anxiety or depression. Autism Spectrum Disorder (ASD) Diagnosis AI algorithms can assist in early ASD diagnosis by analyzing video and audio recordings of children's behavior. These tools help identify subtle behavioral markers, enabling earlier intervention and treatment. Personalized Therapy AI-based therapy platforms use personalized algorithms to adapt therapeutic interventions based on an individual's progress and needs. These platforms can provide continuous support and resources for patients, making therapy more accessible and effective. Virtual Reality Therapy Virtual reality (VR) combined with AI can create immersive therapeutic environments for treating phobias, PTSD, and social anxiety. AI algorithms can adapt VR scenarios in real-time to suit the patient's progress and comfort level. Data Analysis AI aids researchers in processing vast amounts of data, including survey responses, brain imaging, and genetic information. Privacy Concerns Collecting and analyzing personal data for AI applications in psychology and behavioral sciences raise significant privacy concerns. Researchers must ensure the ethical use and protection of sensitive information. Bias and Fairness AI algorithms can inherit biases present in training data, potentially leading to biased assessments or recommendations. Efforts to mitigate bias and ensure fairness in AI applications are crucial. Transparency and Accountability AI-driven decisions in psychology and behavioral sciences should be transparent and subject to accountability. Patients and practitioners should understand how AI algorithms operate and make decisions. AI applications in psychological and behavioral sciences have the potential to transform the field by enhancing diagnosis, therapy, and research. However, these advancements come with ethical challenges that require careful consideration. Collaboration between AI researchers and psychological and behavioral science experts is essential to harness AI's full potential while upholding ethical standards and privacy protections. The future of AI in psychology and behavioral sciences holds great promise, but it must be navigated with caution and responsibility.

Keywords: artificial intelligence, psychological sciences, behavioral sciences, diagnosis and therapy, ethical considerations

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Authors: Yu-Lin Chen, Kimberly Koester, Marissa Raymond-Flesh, Anika Thapar, Jay Thapar

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Purpose: Effectively communicating adolescent health topics to teens and their parents is crucial. This study emphasizes critically evaluating the optimal use of artificial intelligence tools (AI), which are increasingly prevalent in disseminating health information. By fostering a deeper understanding of AI voice preference in the context of health, the research aspires to have a ripple effect, enhancing the collective health literacy and decision-making capabilities of both teenagers and their parents. This study explores AI voices' potential within health learning modules for annual well-child visits. We aim to identify preferred voice characteristics and understand factors influencing perceived trustworthiness, ultimately aiming to improve health literacy and decision-making in both demographics. Methods: A cross-sectional study assessed preferences and trust perceptions of AI voices in learning modules among teens (11-18) and their parents/guardians in Northern California. The study involved the development of four distinct learning modules covering various adolescent health-related topics, including general communication, sexual and reproductive health communication, parental monitoring, and well-child check-ups. Participants were asked to evaluate eight AI voices across the modules, considering a set of six factors such as intelligibility, naturalness, prosody, social impression, trustworthiness, and overall appeal, using Likert scales ranging from 1 to 10 (the higher, the better). They were also asked to select their preferred choice of voice for each module. Descriptive statistics summarized participant demographics. Chi-square/t-tests explored differences in voice preferences between groups. Regression models identified factors impacting the perceived trustworthiness of the top-selected voice per module. Results: Data from 104 participants (teen=63; adult guardian = 41) were included in the analysis. The mean age is 14.9 for teens (54% male) and 41.9 for the parent/guardian (12% male). At the same time, similar voice quality ratings were observed across groups, and preferences varied by topic. For instance, in general communication, teens leaned towards young female voices, while parents preferred mature female tones. Interestingly, this trend reversed for parental monitoring, with teens favoring mature male voices and parents opting for mature female ones. Both groups, however, converged on mature female voices for sexual and reproductive health topics. Beyond preferences, the study delved into factors influencing perceived trustworthiness. Interestingly, social impression and sound appeal emerged as the most significant contributors across all modules, jointly explaining 71-75% of the variance in trustworthiness ratings. Conclusion: The study emphasizes the importance of catering AI voices to specific audiences and topics. Social impression and sound appeal emerged as critical factors influencing perceived trustworthiness across all modules. These findings highlight the need to tailor AI voices by age and the specific health information being delivered. Ensuring AI voices resonate with both teens and their parents can foster their engagement and trust, ultimately leading to improved health literacy and decision-making for both groups. Limitations and future research: This study lays the groundwork for understanding AI voice preferences for teenagers and their parents in healthcare settings. However, limitations exist. The sample represents a specific geographic location, and cultural variations might influence preferences. Additionally, the modules focused on topics related to well-child visits, and preferences might differ for more sensitive health topics. Future research should explore these limitations and investigate the long-term impact of AI voice on user engagement, health outcomes, and health behaviors.

Keywords: artificial intelligence, trustworthiness, voice, adolescent

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Authors: Dimitra C. Banti, Gesthimani Liona, Petros Samaras, Manasis Mitrakas

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Municipal and industrial wastewaters are often treated biologically, by the activated sludge process (ASP). The ASP not only requires large aeration and sedimentation tanks, but also generates large quantities of excess sludge. An alternative technology is the membrane bioreactor (MBR), which replaces two stages of the conventional ASP—clarification and settlement—with a single, integrated biotreatment and clarification step. The advantages offered by the MBR over conventional treatment include reduced footprint and sludge production through maintaining a high biomass concentration in the bioreactor. Notwithstanding these advantages, the widespread application of the MBR process is constrained by membrane fouling. Fouling leads to permeate flux decline, making more frequent membrane cleaning and replacement necessary and resulting to increased operating costs. In general, membrane fouling results from the interaction between the membrane material and the components in the activated sludge liquor. The latter includes substrate components, cells, cell debris and microbial metabolites, such as Extracellular Polymeric Substances (EPS) and Sludge Microbial Products (SMPs). The challenge for effective MBR operation is to minimize the rate of Transmembrane Pressure (TMP) increase. This can be achieved by several ways, one of which is the addition of specific additives, that enhance the coagulation and flocculation of compounds, which are responsible for fouling, hence reducing biofilm formation on the membrane surface and limiting the fouling rate. In this project the effectiveness of a non-commercial composite coagulant was studied as an agent for fouling control in a lab scale MBR system consisting in two aerated tanks. A flat sheet membrane module with 0.40 um pore size was submerged into the second tank. The system was fed by50 L/d of municipal wastewater collected from the effluent of the primary sedimentation basin. The TMP increase rate, which is directly related to fouling growth, was monitored by a PLC system. EPS, MLSS and MLVSS measurements were performed in samples of mixed liquor; in addition, influent and effluent samples were collected for the determination of physicochemical characteristics (COD, BOD5, NO3-N, NH4-N, Total N and PO4-P). The coagulant was added in concentrations 2, 5 and 10mg/L during a period of 2 weeks and the results were compared with the control system (without coagulant addition). EPS fractions were extracted by a three stages physical-thermal treatment allowing the identification of Soluble EPS (SEPS) or SMP, Loosely Bound EPS (LBEPS) and Tightly Bound EPS (TBEPS). Proteins and carbohydrates concentrations were measured in EPS fractions by the modified Lowry method and Dubois method, respectively. Addition of 2 mg/L coagulant concentration did not affect SEPS proteins in comparison with control process and their values varied between 32 to 38mg/g VSS. However a coagulant dosage of 5mg/L resulted in a slight increase of SEPS proteins at 35-40 mg/g VSS while 10mg/L coagulant further increased SEPS to 44-48mg/g VSS. Similar results were obtained for SEPS carbohydrates. Carbohydrates values without coagulant addition were similar to the corresponding values measured for 2mg/L coagulant; the addition of mg/L coagulant resulted to a slight increase of carbohydrates SEPS to 6-7mg/g VSS while a dose of 10 mg/L further increased carbohydrates content to 9-10mg/g VSS. Total LBEPS and TBEPS, consisted of proteins and carbohydrates of LBEPS and TBEPS respectively, presented similar variations by the addition of the coagulant. Total LBEPS at 2mg/L dose were almost equal to 17mg/g VSS, and their values increased to 22 and 29 mg/g VSS during the addition of 5 mg/L and 10 mg/L of coagulant respectively. Total TBEPS were almost 37 mg/g VSS at a coagulant dose of 2 mg/L and increased to 42 and 51 mg/g VSS at 5 mg/L and 10 mg/L doses, respectively. Therefore, it can be concluded that coagulant addition could potentially affect microorganisms activities, excreting EPS in greater amounts. Nevertheless, EPS increase, mainly SEPS increase, resulted to a higher membrane fouling rate, as justified by the corresponding TMP increase rate. However, the addition of the coagulant, although affected the EPS content in the reactor mixed liquor, did not change the filtration process: an effluent of high quality was produced, with COD values as low as 20-30 mg/L.

Keywords: extracellular polymeric substances, MBR, membrane fouling, EPS

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Authors: Mara Getachew Zenebe, Luuk Fleskens, Abdu Obieda Ahmed

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This paper seeks to advance our scientific understanding of optimizing flood utilization in regions impacted by climate change, with a focus on enhancing agricultural productivity through effective irrigation management. The study was conducted as part of a three-year (2021 to 2023) USAID-supported initiative aimed at promoting Economic Growth and Peace in the Gash Agricultural Scheme (GAS), situated in Sudan's water-stressed Eastern region. GAS is the country's largest flood-irrigated scheme, covering 100,800 hectares of cultivable land, with a potential to provide the food security needs of over a quarter of a million agro-pastoral community members. GAS relies on the Gash River, which sources its water from high-intensity rainfall events in the highlands of Ethiopia and Eritrea. However, climate change and variations in these highlands have led to increased variability in the Gash River's flow. The study conducted water balance analyses based on a ten-year dataset of the annual Gash River flow, irrigated area; as well as the evapotranspiration demand of the major sorghum crop. Data collection methods included field measurements, surveys, remote sensing, and CropWat modelling. The water balance assessment revealed that the existing three-year rotation-based irrigation system management, capping cultivated land at 33,000 hectares annually, is excessively risk-averse. While this system reduced conflicts among the agro-pastoral communities by consistently delivering on the land promised to be annually cultivated, it also increased GAS's vulnerability to flood damage due to several reasons. The irrigation efficiency over the past decade was approximately 30%, leaving significant unharnessed floodwater that caused damage to infrastructure and agricultural land. The three-year rotation resulted in inadequate infrastructural maintenance, given the destructive nature of floods. Additionally, it led to infrequent land tillage, allowing the encroachment of mesquite trees hindering major sorghum crop growth. Remote sensing data confirmed that mesquite trees have overtaken 70,000 hectares in the past two decades, rendering them unavailable for agriculture. The water balance analyses suggest shifting to a two-year rotation, covering approximately 50,000 hectares annually while maintaining risk aversion. This shift could boost GAS's annual sorghum production by two-thirds, exceeding 850,000 tons. The scheme's efficiency can be further enhanced through low-cost on-farm interventions. Currently, large irrigation plots that range from 420 to 756 hectares are irrigated with limited water distribution guidance, leading to uneven irrigation. As demonstrated through field trials, implementing internal longitudinal bunds and horizontal deflector bunds can increase adequately irrigated parts of the irrigation plots from 50% to 80% and thus nearly double the sorghum yield to 2 tons per hectare while reducing the irrigation duration from 30 days to a maximum of 17 days. Flow measurements in 2021 and 2022 confirmed that these changes sufficiently meet the sorghum crop's water requirements, even with a conservative 60% field application efficiency assumption. These insights and lessons from the GAS on enhancing agricultural resilience and sustainability in the face of climate change are relevant to flood-based livelihood systems globally.

Keywords: climate change, irrigation management and productivity, variable flood flows, water balance analysis

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Authors: Mirijam Vrabec, Marian Janak, Bojan Ambrozic, Angelja K. Surca, Nastja Rogan Smuc, Nina Zupancic, Saso Sturm

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Natural microdiamonds and moissanite (SiC) can form during the orogenic events under ultrahigh-pressure metamorphic conditions (UHP), when parts of Earth’s crust are subducted to extreme depths. So far, such processes were identified only in few places on the Earth, and therefore, represent unique opportunity to study the evolution of the Earth’s deep interior. An important discovery of microdiamonds and moissanite was reported from Pohorje, (Slovenia), where they occurred as single or polyphase inclusions in garnets. Metasedimentary rocks from Pohorje are predominantly gneisses representing parts of the Austroalpine metamorphic units of the Eastern Alps. During Cretaceous orogeny, (ca. 95–92 Ma) continental crustal rocks were deeply subducted to the mantle depths (below 100 km) and metamorphosed at pressures exceeding 3.5 GPa and temperatures between 800–850 °C. Microstructural and phase analysis of the inclusions as well as detailed elemental analysis of host garnets were carried out combining several analytical techniques: optical microscope in plane polarized transmitted light, electron probe microanalysis (EPMA) with wavelength-dispersive x-ray spectrometry (WDS) and field-emission scanning microscope (FEG-SEM) with energy-dispersive x-ray spectroscopy (EDS). Micro-Raman analysis revealed sharp, first order diamond bands sometimes accompanied by graphite bands implying that transformation of diamond back to graphite occurred. To study the chemical and crystallographic relationship between microdiamonds and co-inclusions, advanced techniques of transmission electron microscopy (TEM) were applied, which included high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), combined with EDS and electron energy-loss spectroscopy (EELS). To prepare electron transparent TEM lamellae selectively a dual-beam Focused Ion Beam/SEM (FIB/SEM) was employed. Detailed study of TEM lamellae, which was cross-sectioned from the highly faceted inclusion body located within the host garnet crystal matrix, revealed rich and rather complex internal structure. Namely, the negative crystal facets of the main inclusion body were typically decorated with up to 1 μm thick amorphous layer, reflecting the general garnet composition with slight variations in Fe/Ca content. Within these layers, ELNES analysis revealed the presence of a 28–30 nm thick layer of amorphous carbon. The very last section of this layer corresponds to composition of SiO2. Within the inclusion, besides diamond and moissanite alumosilicate mineral with pronounced layered structure, iron sulfides and chlorine were identified under TEM and CO2 and CH4 using Raman. Moissanite is found as single crystal or composed from numerous highly textured nano-crystals with the average size of 10 nm. Moissanite inclusions were found embedded inside the amorphous crust implying that moissanite crystalized well before the deposition of the amorphous layer. From the microstructural, crystallographic and chemical observations so far we can deduce, that polyphase inclusions in diamond bearing garnets from Pohorje most probably crystallized from reduced supercritical fluids. Based on layered interface structure of the host mineral multiphase process of crystallization is possible. The presence of microdiamonds and moissanite in rocks from Pohorje demonstrates that these parts of the Eastern Alps were subducted to extreme depths, and were subsequently exhumed back to the Earth's surface without complete breakdown of UHP mineral phases, allowing a rear and exceptional opportunity to study them in-situ.

Keywords: diamond, fluid inclusions, moissanite, TEM, UHP metamorphism.

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Authors: Delia Gabriela Moisa, Demos Parapanos, Tim Heap

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The tourism sector is mainly comprised of small and medium-sized tourism enterprises (SMEs), representing approximately 80% of global businesses in this field. These entities require focused attention and support to address challenges, ensuring their competitiveness and relevance in a dynamic industry characterized by continuously changing customer preferences. To address these challenges, it becomes imperative to consider not only socio-demographic factors but also delve into the intricate interplay of psychological elements influencing consumer behavior. This study investigates the impact of personality traits and travel motivations on visitor activities in Cumbria, United Kingdom, an iconic region marked by UNESCO World Heritage Sites, including The Lake District National Park and Hadrian's Wall. With a £4.1 billion tourism industry primarily driven by SMEs, Cumbria serves as an ideal setting for examining the relationship between tourist psychology and activities. Employing the Big Five personality model and the Travel Career Pattern motivation theory, this study aims to explain the relationship between psychological factors and tourist activities. The study further explores SME perspectives on personality-based market segmentation, providing strategic insights into addressing evolving tourist preferences.This pioneering mixed-methods study integrates quantitative data from 330 visitor surveys, subsequently complemented by qualitative insights from tourism SME representatives. The findings unveil that socio-demographic factors do not exhibit statistically significant variations in the activities pursued by visitors in Cumbria. However, significant correlations emerge between personality traits and motivations with preferred visitor activities. Open-minded tourists gravitate towards events and cultural activities, while Conscientious individuals favor cultural pursuits. Extraverted tourists lean towards adventurous, recreational, and wellness activities, while Agreeable personalities opt for lake cruises. Interestingly, a contrasting trend emerges as Extraversion increases, leading to a decrease in interest in cultural activities. Similarly, heightened Agreeableness corresponds to a decrease in interest in adventurous activities. Furthermore, travel motivations, including nostalgia and building relationships, drive event participation, while self-improvement and novelty-seeking lead to adventurous activities. Additionally, qualitative insights from tourism SME representatives underscore the value of targeted messaging aligned with visitor personalities for enhancing loyalty and experiences. This study contributes significantly to scholarship through its novel framework, integrating tourist psychology with activities and industry perspectives. The proposed conceptual model holds substantial practical implications for SMEs to formulate personalized offerings, optimize marketing, and strategically allocate resources tailored to tourist personalities. While the focus is on Cumbria, the methodology's universal applicability offers valuable insights for destinations globally seeking a competitive advantage. Future research addressing scale reliability and geographic specificity limitations can further advance knowledge on this critical relationship between visitor psychology, individual preferences, and industry imperatives. Moreover, by extending the investigation to other districts, future studies could draw comparisons and contrasts in the results, providing a more nuanced understanding of the factors influencing visitor psychology and preferences.

Keywords: personality trait, SME, tourist behaviour, tourist motivation, visitor activity

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Authors: Stephan Treuke

Abstract:

The paper analyses the neighbourhood effects on the economic mobility of the inhabitants of three segregated communities of Salvador (Brazil), in other words, the socio-economic advantages and disadvantages affecting the lives of poor people due to their embeddedness in specific socio-residential contexts. Recent studies performed in Brazilian metropolis have concentrated on the structural dimensions of negative externalities in order to explain neighbourhood-level variations in a field of different phenomena (delinquency, violence, access to the labour market and education) in spatial isolated and socially homogeneous slum areas (favelas). However, major disagreement remains whether the contiguity between residents of poor neighbourhoods and higher-class condominio-dwellers provides structures of opportunities or whether it fosters socio-spatial stigmatization. Based on a set of interviews, investigating the variability of interpersonal networks and their activation in the struggle for economic inclusion, the study confirms that the proximity of Nordeste de Amaralina to middle-/upper-class communities affects positively the access to labour opportunities. Nevertheless, residential stigmatization, as well as structures of social segmentation, annihilate these potentials. The lack of exposition to individuals and groups extrapolating from the favela’s social, educational and cultural context restricts the structures of opportunities to local level. Therefore, residents´ interpersonal networks reveal a high degree of redundancy and localism, based on bonding ties connecting family and neighbourhood members. The resilience of segregational structures in Plataforma contributes to the naturalization of social distance patters. It’s embeddedness in a socially homogeneous residential area (Subúrbio Ferroviário), growing informally and beyond official urban politics, encourages the construction of isotopic patterns of sociability, sharing the same values, social preferences, perspectives and behaviour models. Whereas it’s spatial isolation correlates with the scarcity of economic opportunities, the social heterogeneity of Fazenda Grande II interviewees and the socialising effects of public institutions mitigate the negative repercussions of segregation. The networks’ composition admits a higher degree of heterophilia and a greater proportion of bridging ties accounting for the access to broader information actives and facilitating economic mobility. The variability observed within the three different scenarios urges to reflect about the responsability of urban politics when it comes to the prevention or consolidation of the social segregation process in Salvador. Instead of promoting the local development of the favela Plataforma, public housing programs priorize technocratic habitational solutions without providing the residents’ socio-economic integration. The impact of negative externalities related to the homogeneously poor neighbourhood is potencialized in peripheral areas, turning its’ inhabitants socially invisible, thus being isolated from other social groups. The example of Nordeste de Amaralina portrays the failing interest of urban politics to bridge the social distances structuring the brazilian society’s rigid stratification model, founded on mecanisms of segmentation (unequal access to labour market and education system, public transport, social security and law protection) and generating permanent conflicts between the two socioeconomically distant groups living in geographic contiguity. Finally, in the case of Fazenda Grande II, the public investments in both housing projects and complementary infrastructure (e.g. schools, hospitals, community center, police stations, recreation areas) contributes to the residents’ socio-economic inclusion.

Keywords: economic mobility, neighborhood effects, Salvador, segregation

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Authors: Guilherme Giacomini, Ana Luiza Menegatti Pavan, Allan Felipe Fattori Alves, Marcela de Oliveira, Fernando Antonio Bacchim Neto, José Ricardo de Arruda Miranda, Seizo Yamashita, Diana Rodrigues de Pina

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The maxillary sinus (MS), part of the paranasal sinus complex, is one of the most enigmatic structures in modern humans. The literature has suggested that MSs function as olfaction accessories, to heat or humidify inspired air, for thermoregulation, to impart resonance to the voice and others. Thus, the real function of the MS is still uncertain. Furthermore, the MS anatomy is complex and varies from person to person. Many diseases may affect the development process of sinuses. The incidence of rhinosinusitis and other pathoses in the MS is comparatively high, so, volume analysis has clinical value. Providing volume values for MS could be helpful in evaluating the presence of any abnormality and could be used for treatment planning and evaluation of the outcome. The computed tomography (CT) has allowed a more exact assessment of this structure, which enables a quantitative analysis. However, this is not always possible in the clinical routine, and if possible, it involves much effort and/or time. Therefore, it is necessary to have a convenient, robust, and practical tool correlated with the MS volume, allowing clinical applicability. Nowadays, the available methods for MS segmentation are manual or semi-automatic. Additionally, manual methods present inter and intraindividual variability. Thus, the aim of this study was to develop an automatic tool to quantity the MS volume in CT scans of paranasal sinuses. This study was developed with ethical approval from the authors’ institutions and national review panels. The research involved 30 retrospective exams of University Hospital, Botucatu Medical School, São Paulo State University, Brazil. The tool for automatic MS quantification, developed in Matlab®, uses a hybrid method, combining different image processing techniques. For MS detection, the algorithm uses a Support Vector Machine (SVM), by features such as pixel value, spatial distribution, shape and others. The detected pixels are used as seed point for a region growing (RG) segmentation. Then, morphological operators are applied to reduce false-positive pixels, improving the segmentation accuracy. These steps are applied in all slices of CT exam, obtaining the MS volume. To evaluate the accuracy of the developed tool, the automatic method was compared with manual segmentation realized by an experienced radiologist. For comparison, we used Bland-Altman statistics, linear regression, and Jaccard similarity coefficient. From the statistical analyses for the comparison between both methods, the linear regression showed a strong association and low dispersion between variables. The Bland–Altman analyses showed no significant differences between the analyzed methods. The Jaccard similarity coefficient was > 0.90 in all exams. In conclusion, the developed tool to quantify MS volume proved to be robust, fast, and efficient, when compared with manual segmentation. Furthermore, it avoids the intra and inter-observer variations caused by manual and semi-automatic methods. As future work, the tool will be applied in clinical practice. Thus, it may be useful in the diagnosis and treatment determination of MS diseases. Providing volume values for MS could be helpful in evaluating the presence of any abnormality and could be used for treatment planning and evaluation of the outcome. The computed tomography (CT) has allowed a more exact assessment of this structure which enables a quantitative analysis. However, this is not always possible in the clinical routine, and if possible, it involves much effort and/or time. Therefore, it is necessary to have a convenient, robust and practical tool correlated with the MS volume, allowing clinical applicability. Nowadays, the available methods for MS segmentation are manual or semi-automatic. Additionally, manual methods present inter and intraindividual variability. Thus, the aim of this study was to develop an automatic tool to quantity the MS volume in CT scans of paranasal sinuses. This study was developed with ethical approval from the authors’ institutions and national review panels. The research involved 30 retrospective exams of University Hospital, Botucatu Medical School, São Paulo State University, Brazil. The tool for automatic MS quantification, developed in Matlab®, uses a hybrid method, combining different image processing techniques. For MS detection, the algorithm uses a Support Vector Machine (SVM), by features such as pixel value, spatial distribution, shape and others. The detected pixels are used as seed point for a region growing (RG) segmentation. Then, morphological operators are applied to reduce false-positive pixels, improving the segmentation accuracy. These steps are applied in all slices of CT exam, obtaining the MS volume. To evaluate the accuracy of the developed tool, the automatic method was compared with manual segmentation realized by an experienced radiologist. For comparison, we used Bland-Altman statistics, linear regression and Jaccard similarity coefficient. From the statistical analyses for the comparison between both methods, the linear regression showed a strong association and low dispersion between variables. The Bland–Altman analyses showed no significant differences between the analyzed methods. The Jaccard similarity coefficient was > 0.90 in all exams. In conclusion, the developed tool to automatically quantify MS volume proved to be robust, fast and efficient, when compared with manual segmentation. Furthermore, it avoids the intra and inter-observer variations caused by manual and semi-automatic methods. As future work, the tool will be applied in clinical practice. Thus, it may be useful in the diagnosis and treatment determination of MS diseases.

Keywords: maxillary sinus, support vector machine, region growing, volume quantification

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Authors: Hosein Maghsoudi

Abstract:

Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

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