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Increased hazards threatening the United Nations Educational, Scientific and Cultural Organization (UNESCO)-designated sites and endangering cultural heritage and community well-being require attention and action. Considering the pivotal role of UNESCO sites in conservation and development, this study assessed their levels of disaster preparedness. The absence of studies assessing disaster awareness, risk perception, and preparedness among UNESCO site actors, as well as the pivotal place of preparedness within the Disaster Risk Management (DRM) cycle justifies this research. Applying the tenets of the Person-Relative-to-Event framework, we hypothesized that a strong positive correlation exists between perceived risks, resources, and disaster preparedness. To collect pertinent data, we employed an embedded mixed-method design and conducted an online questionnaire survey yielding 141 responses from 59 countries. From the results of relevant analyses, wildfires, floods, and droughts are top hazards occurring frequently in UNESCO sites, with significant concerns about pollution and habitat loss during future events. Smartphones emerged as the most available crucial DRM resource, with higher availability of DRM resources correlating positively and significantly with sites’ preparedness. Our findings contribute valuable insights to address missing links for disaster-ready and resilient UNESCO sites, promoting their preservation for future generations.

Abstract Graphene nanoribbons (GNRs) of precise size and shape, critical for controlling electronic properties and future device applications, can be realized via precision synthesis on surfaces using rationally designed molecular precursors. Fluorine-bearing precursors have the potential to form GNRs on nonmetallic substrates suitable for device fabrication. Here, we investigate the deposition temperature-mediated growth of a new fluorine-bearing precursor, 6,11-diiodo-1,4-bis(2-fluorophenyl)-2,3-diphenyltriphenylene (C42H24F2I2), into helically shaped polymer intermediates and chevron-type GNRs on Au(111) by combining scanning tunneling microscopy, X-ray photoelectron spectroscopy, and density functional theory simulations. The fluorinated precursors do not adsorb on the Au(111) surface at lower temperatures, necessitating an optimum substrate temperature to achieve maximum polymer and GNR lengths. We compare the adsorption behavior with that of pristine chevron precursors and discuss the effects of C-H and C-F bonds. The results elucidate the growth mechanism of GNRs with fluorine-bearing precursors and establish a foundation for future synthesis of GNRs on nonmetallic substrates.

The KRAS gene is mutated in approximately 45% of colorectal cancer patients. There are currently very few targeted treatments or therapies equipped to directly inhibit KRAS due to its unusual structural intricacies. Erlotinib, an EGFR inhibitor, has previously been demonstrated to reduce cell viability by inducing autophagy in lung cancer cell lines with varying EGFR mutations. In contrast to lung cancer cells, evidence is provided herein for the first time that erlotinib treatment in colorectal cancer (CRC) cell lines reduces autophagy and still results in decreased cell viability. However, the effects of erlotinib in CRC cell lines containing a wildtype KRAS gene were different than in cells carrying a mutant KRAS gene. We show that there is significantly more downregulation of autophagy in KRAS mutant CRC cells compared to KRAS wildtype cells, both at transcriptional and translational levels, suggesting that the KRAS mutation is advantageous for cancer growth, even in the presence of erlotinib. Cell viability results determined that KRAS wildtype CRC cells had significantly more cell death compared to KRAS mutant cells. Using patient mRNA datasets, we showed that there was a significant correlation between the presence of the KRAS mutation and the expression of autophagy proteins. Additionally, through molecular dynamics simulations, we develop a blueprint for KRAS and autophagy protein interaction and the impact of the KRAS mutation on autophagy protein regulation. Overall, this is the first report of erlotinib treatment in CRC cells that assesses autophagy, and we demonstrate that autophagy activity is downregulated in these cells. This effect is not only greater in cells carrying a KRAS mutation compared to wildtype cells, but the KRAS mutant cells also have increased cell viability compared to wildtype cells. We hypothesize that the difference in cell viability and autophagy expression between KRAS mutant and KRAS wildtype cells after treatment with erlotinib can be of therapeutic value to treat CRC patients carrying KRAS mutations.

Abstract Background Helicobacter pylori infection is prevalent worldwide and can lead to peptic ulcer disease (PUD) and gastric cancer. Effective diagnosis and treatment of H. pylori infection by gastroenterologists and family physicians is crucial. However, there are differing views on optimal diagnosis and treatment. The objective of this study is to understand the impressions of Canadian physicians regarding H. pylori diagnosis and treatment and whether impressions differ between gastroenterologists and family physicians. A second objective is to understand physician perspectives on rising antibiotic resistance and how that guides empiric management. Methods A survey facilitated via REDCap was administered to Canadian gastroenterologists and family physicians. A total of 105 participants completed the survey, including 43 gastroenterologists and 62 family physicians. Gastroenterologists were recruited from across the country and family physicians were recruited from Manitoba. Results For diagnosis of H. pylori, 67% of gastroenterologists reported endoscopic biopsies for histology assessment as most common and 73% of family physicians reported serology as their main diagnostic test. While nearly all gastroenterologists believed antibiotic resistance to be a problem, nearly one quarter of family physicians did not believe it was a problem. Conclusions There is variability in practices among both gastroenterologists and family physicians regarding diagnosis of H. pylori infection. There was consensus that local antibiotic resistance patterns should guide management. If known, the degree and patterns of antibiotic resistance could bring a more uniform consensus to H. pylori management. Greater education of physicians, especially family physicians regarding management of H pylori is needed.

Abstract Engaging young people in research is a promising approach to tackling issues like chronic disease prevention. Our involvement as youth advisors provided valuable experiences, including being at the forefront of change and learning to work within a research team. Furthermore, our experience provides greater insight and learnings for future youth engagement in research.

Introdução: Acidentes com serpentes são um problema de saúde pública no Brasil, classificados como doença negligenciada. Foram notificados 29.543 casos de acidentes ofídicos em 2022, e os maiores coeficientes de incidência por ofidismo foram observados na Região Norte (55,26/100 mil hab.), cerca de 4,1 vezes o coeficiente de incidência do Brasil. No Estado de Roraima, houve a maior incidência, 68,64/100 mil hab., principalmente devido à sua população indígena significativa e à extensa cobertura da Floresta Amazônica na região. As principais serpentes de importância médica do Brasil são dos genêros Bothrops (jararaca), Crotalus (cascavéis), Lachesis (surucucu-pico-de-jaca), Micrurus (corais-verdadeiras). Objetivo: O objetivo desse estudo é conhecer o perfil clínico-epidemiológico dos acidentes ofídicos ocorridos em Roraima. Método: Trata-se de um estudo baseado em análises de casos e descritivo, envolvendo indivíduos acometidos por acidentes ofídicos e internados no Hospital Geral de Roraima Rubens de Souza Bento (HGR), que deram entrada durante o período de julho de 2023 a abril de 2024. Este estudo foi devidamente aprovado pelo CEP/CONEP (CAAE 24120719.5.0000.5302). Resultados: Foram coletados 15 casos, sendo 11 pacientes foram afetados por serpentes do gênero Bothrops, com 3 casos leves, 4 moderados e 4 graves. Por outro lado, foram registrados 2 casos moderados envolvendo serpentes da gênero Crotalus. Além disso, houve 2 casos classificados como indefinidos. Em relação aos dados epidemiológicos, 90% dos pacientes eram do sexo masculino, com idades entre 18 e 58 anos. Todos não eram residentes de Boa Vista, sendo 73% de etnias indígenas e o restante de cor parda. Os acidentes ocorreram principalmente nos municípios de Alto Alegre, Cantá e Amajari. Ao todo, 07 pacientes relataram ter usado um ''antídoto caseiro'' chamado ''Específico Pessoa''. Outras medidas pré-atendimento foram relatadas, como lavar com água e sabão, realizar torniquete e furar o local da picada com ponta de faca. Quanto ao uso da escala visual da dor, 90% dos pacientes indicaram o nível máximo de dor, que é 10. Conclusão: Observou-se predominância de acidentes botrópicos sobre os crotálicos, em consonância com o padrão nacional. Os indígenas, com baixo nível socioeconômico e educacional e escasso conhecimento sobre acidentes ofídicos, destacam-se como a população mais afetada. A análise dos casos revelou a ausência de um protocolo único de abordagem, com variabilidade na pré-medicação, antibióticos e critérios de internação.

IntroductionThe differential ratio of nonsynonymous to synonymous nucleotide substitutions (dN/dS) is a common measure of the rate of structural evolution in proteincoding genes. In addition, we recently suggested that the proportion of transposable elements in gene promoters that host functional genomic sites serves as a marker of the rate of regulatory evolution of genes. Such functional genomic regions may include transcription factor binding sites and modified histone binding loci.MethodsHere, we constructed a model of the human interactome based on 600,136 documented molecular interactions and investigated the overall relationship between the number of interactions of each protein and the rate of structural and regulatory evolution of the corresponding genes.ResultsBy evaluating a total of 4,505 human genes and 1,936 molecular pathways we found a general correlation between structural and regulatory evolution rate metrics (Spearman 0.08–0.16 and 0.25–0.37 for gene and pathway levels, respectively, p < 0.01). Further exploration revealed in the established human interactome model lack of correlation between the rate of gene regulatory evolution and the number of protein interactions on gene level, and weak negative correlation (∼0.15) on pathway level. We also found a statistically significant negative correlation between the rate of gene structural evolution and the number of protein interactions (Spearman −0.11 and −0.3 for gene and pathway levels, respectively, p < 0.01).DiscussionOur result suggests stronger structural rather than regulatory conservation of genes whose protein products have multiple interaction partners.

Latinoamérica continua con los esfuerzos para producir universidades orientadas a la investigación respondiendo a los desafíos actuales en una región con menor tradición académica y ejerciendo presión para que estas instituciones tengan producciones científicas de alto impacto y ocupen lugares estelares en los rankings tanto nacionales como internacionales. Bajo ese contexto, este estudio analizó el caso de la producción científica de la Escuela Superior Politécnica del Litoral (ESPOL), una institución pública de investigación ecuatoriana, para contrastar hipótesis sobre sus contribuciones intelectuales y sobre las mediciones de calidad e impacto utilizando un modelo de regresión con Mínimos Cuadrados Ordinarios. Los hallazgos de las contribuciones intelectuales de esta institución mostraron que la antigüedad y extensión están significativamente relacionados con mayores citas. Los artículos publicados en revista de alto impacto, la cantidad de autores y sus distancias regionales tienen un efecto positivo sobre el número de citas y, finalmente, en términos de brecha de género no hubo resultados significativos.

IntroductionAdoptive cell therapy using TCR-engineered T-cells is one of the most effective strategies against tumor cells. The TCR T-cell approach has been well tested against a variety of blood neoplasms but is yet to be deeply tested against solid tumors. Among solid tumors, cancer-testis antigens are the most prominent targets for tumor-specific therapy, as they are usually found on cells that lie behind blood-tissue barriers.MethodsWe have employed a novel efficient protocol for MAGE-A3-specific T-cell clonal expansion, performed single-cell multi-omic analysis of the expanded T-cells via BD Rhapsody, engineered a selected T-cell receptor into a lentiviral construct, and tested it in an in vitro LDH-cytotoxicity test.Results and discussionWe have observed a 191-fold increase in the MAGE-A3-specific T-cell abundance, obtained a dominant T-cell receptor via single-cell multi-omic BD Rhapsody data analysis in the TCRscape bioinformatics tool, and observed potent cytotoxicity of the dominant-clonotype transduced TCR T-cells against a MAGE-A3-positive tumor. We have demonstrated the efficiency of our T-cell enrichment protocol in obtaining potent anti-tumor T-cells and their T-cell receptors, especially when paired with the modern single-cell analysis methods.

Проведены исследования возможностей аугментации (искусственного размножения) обучающих данных в задаче классификации с использованием деформирующих преобразований обрабатываемых изображений. Представлены математическая модель и быстродействующий алгоритм выполнения деформирующего преобразования изображения, при использовании которых исходное изображение преобразуется с сохранением своей структурной основы и отсутствием краевых эффектов. Предложенный алгоритм используется для аугментации наборов изображений в задаче классификации, содержащих относительно небольшое количество обучающих примеров. Аугментация исходной выборки осуществляется в два этапа, включающих зеркальное отображение и деформирующее преобразование каждого исходного изображения. Для проверки эффективности подобной техники аугментации в статье проводится обучение нейронных сетей – классификаторов различного вида: сверточных сетей стандартной архитектуры (convolutional neural network, CNN) и сетей с остаточными связями (deep residual network, DRN). Особенностью реализуемого подхода при решении рассматриваемой задачи является также отказ от использования предобученных нейронных сетей с большим количеством слоев и дальнейшим переносом обучения, поскольку их применение несет за собой затраты с точки зрения используемого вычислительного ресурса. Показано, что эффективность классификации изображений при реализации предложенного метода аугментации обучающих данных на выборках малого и среднего объема повышается до статистически значимых значений используемой метрики.

Abstract Malaria ranks high among prevalent and ravaging infectious diseases in sub-Saharan Africa (SSA). The negative impacts, disease burden, and risk are higher among children and pregnant women as part of the most vulnerable groups to malaria in Nigeria. However, the burden of malaria is not even in space and time. This study explores the spatial variability of malaria prevalence among children under five years (U5) in medium-sized rapidly growing city of Akure, Nigeria using model-based geostatistical modeling (MBG) technique to predict U5 malaria burden at a 100 × 100 m grid, while the parameter estimation was done using Monte Carlo maximum likelihood method. The non-spatial logistic regression model shows that U5 malaria prevalence is significantly influenced by the usage of insecticide-treated nets—ITNs, window protection, and water source. Furthermore, the MBG model shows predicted U5 malaria prevalence in Akure is greater than 35% at certain locations while we were able to ascertain places with U5 prevalence > 10% (i.e. hotspots) using exceedance probability modelling which is a vital tool for policy development. The map provides place-based evidence on the spatial variation of U5 malaria in Akure, and direction on where intensified interventions are crucial for the reduction of U5 malaria burden and improvement of urban health in Akure, Nigeria.

Summary: Monoclonal antibodies (mAbs) targeting bacterial virulence factors may represent promising therapeutics in the fight against severe bacterial infections. Here, we present an approach for developing human-derived antibodies targeting the type III secretion system (T3SS) of Pseudomonas aeruginosa (PA) by neutralizing the function of the T3SS-tip protein PcrV. The protocol involves identifying individuals with protective antibodies, isolating PcrV-specific B cells from these individuals, and producing and testing anti-PcrV mAbs derived from single B cells.For complete details on the use and execution of this protocol, please refer to Simonis et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Background Wait times at Canadian multidisciplinary pain clinics have been reported as excessive for nearly 2 decades.Aims The aim of this study was to gain insight into the patient experience of waiting for chronic pain specialty care.Methods A cross-sectional survey of new patients waiting for an appointment was conducted in six multidisciplinary pain clinics, including one pediatric clinic, in Ontario, Quebec, and Manitoba between February 2020 and October 2022. Participants were asked about the length of time they waited for their appointment since being referred, their quality of life, health care professionals seen while waiting, and an open-ended question, “Is there anything else you’d like to tell us?”Results Among the 493 adult and 100 pediatric respondents, 53% of adults and 82% of children reported wait times under 6 months, whereas 22% of adults and 4% of children waited longer than a year. Between 52% and 63% of adults and 29% to 48% of children reported being affected by chronic pain “quite a bit” or “extremely” on measures of quality of life. The most visited health care professionals while waiting for a pain clinic appointment were family doctors/nurse practitioners for adults and physiotherapists for children. Qualitative analysis of open-ended question responses revealed eight themes: system navigation issues, administrative issues, decreased quality of life, distress, self-advocacy, coping strategies, communication, and distrust.Conclusions Our findings provide real-time regional snapshots into the impact of long wait times experienced by Canadians living with chronic pain. There is an urgent need to better support patients during the waiting period. Expanding technologies such as electronic consultation hold great promise.

Abstract Creating a diverse dipolar microenvironment around the active site is of great significance for the targeted induction of intermediate behaviors to achieve complicated chemical transformations. Herein, an efficient and general strategy is reported to construct hypercross‐linked polymers (HCPs) equipped with tunable dipolar microenvironments by knitting arene monomers together with dipolar functional groups into porous network skeletons. Benefiting from the electron beam irradiation modification technique, the catalytic sites are anchored in an efficient way in the vicinity of the microenvironment, which effectively facilitates the processing of the reactants delivered to the catalytic sites. By varying the composition of the microenvironment scaffold structure, the contact and interaction behavior with the reaction participants can be tuned, thereby affecting the catalytic activity and selectivity. As a result, the framework catalysts produced in this way exhibit excellent catalytic performance in the synthesis of glycinate esters and indole derivatives. This manipulation is reminiscent of enzymatic catalysis, which adjusts the internal polarity environment and controls the output of products by altering the scaffold structure.

The RAS genes which code for KRAS, HRAS, and NRAS are three of the most frequently mutated oncogenes responsible for cancer deaths. Tumorigenesis is one of the most significant outcomes of deregulation of RAS GTPases. Although the structures have been extensively studied, there is still more to be discovered about the actual binding conformations of the three isoforms, especially when mutated, to design an inhibitory drug. Recent studies have identified important interactions between the three isoforms that affect the oncogenic strength of the others when they are mutated. In this study, we utilize molecular dynamics simulations to examine the modifications of the structural property, mechanism, and kinetic energy of KRAS when interacting individually and with HRAS and NRAS. Notably, we found that WT-KRAS’ orientation when bound to WT-HRAS vs. WT-NRAS is rotated 180°, with mutants demonstrating a similar binding pattern. The binding sites of the isoforms with KRAS share similarities with those involved in the GDP/GTP active site and site of KRAS dimerization. Thus, the isoform interaction can serve as an inhibitory method of KRAS actions. This study advances the understanding of inhibiting RAS-driven cancers through a novel isoform interaction approach only recently discovered, which has been proven to be an effective alternate therapeutic approach. We developed a blueprint of the interaction which would be beneficial in the development of KRAS mutant-specific and pan-KRAS mutant inhibitory drugs that mimic the isoform interactions. Our results support the direct interaction inhibition mechanism of mutant KRAS when bound to WT-HRAS and WT-NRAS by the isoforms’ hypervariable region binding to the G-domain of KRAS. Furthermore, our results support the approach of reducing the effects of oncogenic KRAS by altering the concentration of the isoforms or a drug alternative based on the overall structural and kinetic stability, as well as the binding strength of the mutant-isoform complexes.

Abstract Accurate quantification of hypersensitive response (HR) programmed cell death is imperative for understanding plant defense mechanisms and developing disease‐resistant crop varieties. Here, a phenotyping platform for rapid, continuous‐time, and quantitative assessment of HR is demonstrated: Parallel Automated Spectroscopy Tool for Electrolyte Leakage (PASTEL). Compared to traditional HR assays, PASTEL significantly improves temporal resolution and has high sensitivity, facilitating detection of microscopic levels of cell death. Validation is performed by transiently expressing the effector protein AVRblb2 in transgenic Nicotiana benthamiana (expressing the corresponding resistance protein Rpi‐blb2) to reliably induce HR. Detection of cell death is achieved at microscopic intensities, where leaf tissue appears healthy to the naked eye one week after infiltration. PASTEL produces large amounts of frequency domain impedance data captured continuously. This data is used to develop supervised machine‐learning (ML) models for classification of HR. Input data (inclusive of the entire tested concentration range) is classified as HR‐positive or negative with 84.1% mean accuracy (F1 score = 0.75) at 1 h and with 87.8% mean accuracy (F1 score = 0.81) at 22 h. With PASTEL and the ML models produced in this work, it is possible to phenotype disease resistance in plants in hours instead of days to weeks.

This paper introduces a novel anomaly detection approach tailored for time series data with exclusive reliance on normal events during training. Our key innovation lies in the application of kernel-density estimation (KDE) to scrutinize reconstruction errors, providing an empirically derived probability distribution for normal events post-reconstruction. This non-parametric density estimation technique offers a nuanced understanding of anomaly detection, differentiating it from prevalent threshold-based mechanisms in existing methodologies. In post-training, events are encoded, decoded, and evaluated against the estimated density, providing a comprehensive notion of normality. In addition, we propose a data augmentation strategy involving variational autoencoder-generated events and a smoothing step for enhanced model robustness. The significance of our autoencoder-based approach is evident in its capacity to learn normal representation without prior anomaly knowledge. Through the KDE step on reconstruction errors, our method addresses the versatility of anomalies, departing from assumptions tied to larger reconstruction errors for anomalous events. Our proposed likelihood measure then distinguishes normal from anomalous events, providing a concise yet comprehensive anomaly detection solution. The extensive experimental results support the feasibility of our proposed method, yielding significantly improved classification performance by nearly 10% on the UCR benchmark data.

Background Effective healthcare innovations are often not scaled up beyond their initial local context. Lack of practical knowledge on how to move from local innovations to large-system improvement hinders innovation and learning capacity in health systems. Studying scale-up processes can lead to a better understanding of how to facilitate the scale-up of interventions. eConsult is a digital health innovation that aims to connect primary care professionals with specialists through an asynchronous electronic consultation. The recent implementation of eConsult in the public health systems of four Canadian jurisdictions provides a unique opportunity to identify different enabling strategies and related factors that promote the scaling up of eConsult across jurisdictions.Methods We conducted a narrative case study in four Canadian provinces, Quebec, Ontario, Manitoba, and Newfoundland & Labrador, over a 3-year period (2018–2021). We observed provincial eConsult committee meetings (n = 65) and national eConsult forums (n = 3), and we reviewed internal documents (n = 93). We conducted semistructured interviews with key actors in each jurisdiction (eg, researchers, primary care professionals, specialists, policy-makers, and patient partners) (n = 40). We conducted thematic analysis guided by the literature on factors and strategies used to scale up innovations.Results We identified a total of 31 strategies related to six key enabling factors to scaling up eConsult, including: (1) multi-actor engagement; (2) relative advantage; (3) knowledge transfer; (4) strong evidence base; (5) physician leadership; and (6) resource acquisition (eg, human, material, and financial resources). More commonly used strategies, such as leveraging research infrastructure and bringing together various actors, were used to address multiple enabling factors.Conclusion Actors used various strategies to scale up eConsult within their respective contexts, and these helped address six key factors that seemed to be essential to the scale-up of eConsult.

Potato is the third most important food crop in the world in terms of adaptability, yield potential, and nutritional advantages. This study aimed to conduct potato breeding work for cultivation in Kazakhstan; potato breeding for further processing into chips with cultivation in the northern regions; and the selection of potatoes for processing into frozen French fries with cultivation in the southern and south-eastern regions. Potato varieties (Fontane, Santana, and Punchy) were used as reference varieties to check molecular markers linked to maturity, tuber shape, and flesh color. A total of 42 potato breeding lines crossed from Yagodnyi 19 and CIP clone 397079-6 were used in this study to identify prospective breeding lines. The research was carried out between 2023 and 2024 and under greenhouse conditions. According to the results of molecular analysis and phenotypic data, 21 breeding lines were identified as prospective potato breeding lines. The majority of these potato breeding lines had a round tuber shape and were recommended for chip processing. Three breeding lines had a long oval tuber shape, making them suitable for French fries. Six breeding lines with short-oval and oval tuber shapes were found for consumer potato processing. It is recommended that the breeding process and studies of biochemical properties are continued in all of these identified potato breeding lines.

Understanding and acting upon risk is notably challenging, and navigating complexity with understandings developed for stable environments may inadvertently build a false sense of safety. Neglecting the potential for non-linear change or “black swan” events – highly impactful but uncommon occurrences – may lead to naive optimisation under assumed stability, exposing systems to extreme risks. For instance, loss aversion is seen as a cognitive bias in stable environments, but it can be an evolutionarily advantageous heuristic when complete destruction is possible. This paper advocates for better accounting of non-linear change in decision-making by leveraging insights from complex systems and psychological sciences, which help to identify blindspots in conventional decision-making and to develop risk mitigation plans that are interpreted contextually. In particular, we propose a framework using attractor landscapes to visualize and interpret complex system dynamics. In this context, attractors are states toward which systems naturally evolve, while tipping points – critical thresholds between attractors – can lead to profound, unexpected changes impacting a system’s resilience and well-being. We present four generic attractor landscape types that provide a novel lens for viewing risks and opportunities, and serve as decision-making contexts. The main practical contribution is clarifying when to emphasize particular strategies – optimisation, risk mitigation, exploration, or stabilization – within this framework. Context-appropriate decision making should enhance system resilience and mitigate extreme risks.

Communities residing in UNESCO-designated sites, characterised by outstanding universal values, face heightened vulnerability during disasters, necessitating innovative Disaster Risk Reduction (DRR) strategies. The critical role of well-equipped UNESCO site actors in DRR necessary for achieving the goals of broader international frameworks such as Agenda 2030 and the Sendai Framework for Disaster Risk Reduction (SFDRR) warrants this needs assessment study. This study uses a descriptive survey design to assess the competency gaps of UNESCO site actors, including managers and staff, for effective utilisation of DRR innovations (DRRI). Employing the Borich Needs Assessment Model and Ranked Discrepancy Model, an online questionnaire garnered 141 responses from 59 countries. Descriptive statistics, significance tests (at p

Background Chronic cough is a frequent reason for seeking consultation with primary care providers. The recent widespread adoption of virtual care offers a promising alternative that can be used to optimize the assessment and management of this condition. The objective of this review was to map and identify the strategies used to assess and/or manage chronic cough virtually, and to explore their impact on cough severity and patient satisfaction with virtual care. Methods A scoping review was conducted in MEDLINE, EMBASE, and CINAHL in May 2023. Research questions were defined based on the Population, Concept, Context mnemonic, and literature search was conducted using a three-step approach. Study selection involved the steps of identification, screening, eligibility, and inclusion. A descriptive synthesis was performed, and quantitative variables were presented as absolute and relative frequencies. Results A total of 4953 studies were identified and seven met the inclusion criteria. The following mHealth and telehealth strategies were identified: diagnostic website, specialized online clinic, online speech language therapy, and remote follow-up to assess the effectiveness of in-person interventions. Results indicated that these virtual strategies can be useful to assess chronic cough, treat, and track chronic cough symptoms. Overall, patients were satisfied with the approaches. Conclusion Although literature is scarce, evidence suggests that virtual strategies for the assessment and management of chronic cough may be effective and are well-received by patients. However, further research is needed to identify the type and characteristics of virtual approaches leading to optimize and facilitate the care of patients with this condition. This will also help develop a strong body of evidence to support their incorporation into guidelines and clinical practice.

This article focuses on software methods for detecting and preventing the introduction of hardware trojans into the topology of integrated circuits at the design stage. An additional recommendation for typical procedures of receiving GDSII files that significantly complicates the introduction of HTs into the topology is to facilitate detection methods by including special self-test structures created after performing transformations of the initial topology and ensuring the effective examination of ICs at the post-manufacture test stage. The proposed method is based on the analysis of synthesis results at the level of netlist description, its subsequent software conversion into a topological drawing, shifting standard cells and filling created voids with special self-test cells. The method is simple to implement during the topology design stage and can be recommended for use in design centres for machine learning of computer-aided design systems.

The furniture manufacturing sector faces significant challenges in machining composite materials, where quality issues such as delamination can lead to substandard products. This study aims to improve the classification of drilled holes in melamine-faced chipboard using Explainable AI (XAI) techniques to better understand and interpret Convolutional Neural Network (CNN) models’ decisions. We evaluated three CNN architectures (VGG16, VGG19, and ResNet101) pretrained on the ImageNet dataset and fine-tuned on our dataset of drilled holes. The data consisted of 8526 images, divided into three categories (Green, Yellow, Red) based on the drill’s condition. We used 5-fold cross-validation for model evaluation and applied LIME and Grad-CAM as XAI techniques to interpret the model decisions. The VGG19 model achieved the highest accuracy of 67.03% and the lowest critical error rate among the evaluated models. LIME and Grad-CAM provided complementary insights into the decision-making process of the model, emphasizing the significance of certain features and regions in the images that influenced the classifications. The integration of XAI techniques with CNN models significantly enhances the interpretability and reliability of automated systems for tool condition monitoring in the wood industry. The VGG19 model, combined with LIME and Grad-CAM, offers a robust solution for classifying drilled holes, ensuring better quality control in manufacturing processes.

This evaluation of deep learning and traditional machine learning methods for tool state recognition in milling processes aims to automate furniture manufacturing. It compares the performance of long short-term memory (LSTM) networks, support vector machines (SVMs), and boosting ensemble decision trees, utilizing sensor data from a CNC machining center. These methods focus on the challenges and importance of feature selection, data preprocessing, and the application of tailored machine learning models to specific industrial tasks. Results show that SVM, with an accuracy of 96%, excels in handling high-dimensional data and robust feature extraction. In contrast, LSTM, which is appropriate for sequential data, is constrained by limited training data and the absence of pre-trained networks. Boosting ensemble decision trees also demonstrate efficacy in reducing model bias and variance. Conclusively, selecting an optimal machine learning strategy is crucial, depending on task complexity and data characteristics, highlighting the need for further research into domain-specific models to improve performance in industrial settings.

Based on published and unpublished archival sources of Yugoslav and Soviet origin, as well as relevant memoirs and historiography, the article examines the course of negotiations between the Yugoslav and Soviet diplomatic representatives in 1918-1924 on mutual recognition and establishment of regular diplomatic relations. The circumstances under which the negotiations began, the reasons that prompted both sides to them, the influence of the interested powers and the Yugoslav Little Entente allies are analyzed. The diplomatic steps taken by the Kingdom of Serbs, Croats and Slovenes immediately after the end of the First World War and aimed at normalizing relations with the largest and most important Slavic country coincided with the efforts of the revolutionary authorities of Russia to break out of isolation and take their place in the international community. Although mutual interests dictated the rapid and effective normalization, a number of factors caused the failure of negotiations. There were fears in Yugoslavia that mutual recognition would lead to a strengthening of the role of Communists in society and that Bolshevik propaganda would undermine the foundations of the existing state system. In addition, the tacit and often direct support of various separatist political groups in Yugoslavia by the Bolsheviks was particularly suspicious. Despite a number of significant political factors and support for rapprochement with the Soviets of a significant part of society, the most influential figures of the Radical Party led by Nikola Pashich, as well as King Alexander Karageorgievich, reacted negatively to this idea.

Сложнейшей задачей защищенных телекоммуникационных систем, использующих симметричное шифрование, в связи с необходимостью предварительной и ресурсоемкой организации секретных каналов доставки ключей сетевым корреспондентам, является управление ключами. Альтернативой выступают методы формирования ключей по открытым каналам связи. В теории информации показано, что эти методы реализуются при условии превышения информационной скорости канала корреспондентов над скоростью канала перехвата нарушителя. Актуализируется поиск методов, обеспечивающих получение информационного преимущества корреспондентов. Цель заключается в определении теоретико-информационных условий формирования виртуальных сети и канала перехвата, для которых обеспечивается лучшее у корреспондентов отношение информационных скоростей по сравнению с отношением исходных сети и канала перехвата. В работе предлагается модель передачи информации, включающая модель связности и метод передачи информации для асимптотических длин кодовых слов. Модель включает трех корреспондентов и отличается введением идеального широковещательного канала в дополнение к широковещательному каналу с ошибками. В модели введен источник «зашумляющей» информации, которая передается по каналу с ошибками, поэтому передача кодовых слов с использованием известного метода случайного кодирования производится по каналу без ошибок. Для асимптотических длин кодовых слов все действия корреспондентов по обработке и передаче информации в модели сведены в предлагаемый метод передачи информации. Использование метода корреспондентами в рамках модели передачи позволяет одновременно сформировать для них новый виртуальный широковещательный канал с информационной скоростью, как и в первоначальном канале с ошибками, а для нарушителя новый виртуальный широковещательный канал перехвата со скоростью меньшей информационной скорости первоначального канала перехвата. Теоретико-информационные условия ухудшения канала перехвата доказывается в утверждении. Практическая значимость полученных результатов заключается в возможности использования последних для оценки информационной эффективности открытого сетевого формирования ключей в предложенной модели передачи информации, а также в развитии известных научных достижений открытого ключевого согласования. Предлагаемая модель передачи может быть полезной для проведения исследований систем управления ключами и защиты информации, передаваемой по открытым каналам. Дальнейшие исследования связаны с теоретико-информационной оценкой сетевой ключевой пропускной способности, представляющей собой потенциальную теоретико-информационную скорость формирования сетевого ключа.

Objective This study explored patient and caregiver expectations and experiences of virtual primary care in Manitoba, Canada. This study focused on accessibility of care, acceptability and perceptions of quality from ‘users’ of primary healthcare services. Due to the rapid implementation of virtual primary care during the COVID-19 pandemic in Canada, patient/public input was largely bypassed. Methods A mixed method was conducted in collaboration with Patient and Caregiver Community Advisors. Data was obtained from 696 surveys and 9 focus groups (n = 41 patients and caregivers). Results Data suggest good acceptance of virtual visits, although considered a new experience despite almost exclusive use of the telephone. Participants preferred more input for choosing the type of visit but experienced less stress, time and inconvenience by using virtual care. There were mixed opinions of quality. More complex visits were associated with incomplete consultations and serve as one exemplar of the limitations due to lack of physical presence or contact. Unique communication skills were required to convey health concerns adequately and accurately. A more transactional approach was perceived from the lack of visual cues and the awkwardness associated with pauses during the phone conversation. Virtual care may be better used for certain circumstances but should encompass patient-centred decision making for when and how. Many expressed interests in video options; technology access and user ability are additional considerations for advancing virtual care. Conclusions The experiences and recommendations from patients and caregivers provide an important contribution to decision-making and integrating and sustaining quality virtual care for patient-centered healthcare service delivery. Keywords: Virtual care experiences, primary care, patient-oriented research, mixed methods, COVID-19.

We live in an urban planet. As the world continues to urbanize, urban development that support the health and wellbeing of city dwellers is far more important than ever before to achieve sustainable development targets. This study explores the complex relationship among urban planning, city growth, and health as critical drivers of sustainable development in the rapidly growing nodal city of Akure, Nigeria. The study provides a four-decade spatio-temporal model of urban Land Use Land Cover (LULC) changes in Akure between the years 1984 and 2023 from acquired Landsat satellite imageries. The result shows more than 20% net change increase in developed LULC classes between the study years. A strong positive correlation exists between the years covered in the analyses and urban development (r = 0.93, p = 0.002), and a strong negative relationship with the forest land use (r = −0.94, p = 0.002) with potential debilitating impacts on residents’ health, green infrastructures and the city’s sustainability in the future. Furthermore, results of key informant interviews (KIIs) of officials of the Ministry of Physical Planning and Urban Development (MPPUD) in Akure, Ondo State, unveil various views on the “place of health” in urban planning practices in Akure. A lack of synergy between urban planners and public health practitioners in the city and limiting scope of functions of urban planning on the impact of health in Akure were observed. Thus, we recommend the integration of a sustainable urban planning approach as a guide to manage the city.

Purpose: In parent-child trios with genome sequencing data, we investigated inherited biallelic deletions to identify known and novel genetic disorders. Methods: We developed a copy-number variations analysis pipeline based on autosomal genome sequencing read depth of Genomics England 100,000 Genomes Project data from 11,754 parent-child trios and additional 18,875 non-trios. A control cohort of 15,440 cancer patients provided independent deletion frequencies. Results: Autosomal recessive (AR) modeling detected 34 distinct rare deletions that were homozygous in the proband and heterozygous in both parents. These inherited biallelic deletions were only detected in 52 trios. These “knockout” regions included 37 genes, having among them 8 with an Online Mendelian Inheritance in Man AR annotation. Deletions of NPHP1, followed by OTOA, both within segmental duplications, were the only recurrent findings explaining phenotypes in a total of 10 and 3 patients, respectively. Recurrent heterozygous NPHP1 deletions were detected in 0.3%-0.5% of controls. We reviewed “knockout” patients for the remaining 29 genes without disease associations and identified SLC66A1 as a likely novel cause for AR rod-cone dystrophy in 4 families. Conclusion: A tailored copy-number variations analysis of genome sequencing trio data shows that biallelic inherited gene deletions are rare, with NPHP1 biallelic deletions causing nephronophthisis the leading finding. We propose SLC66A1 as a novel cause for AR retinopathy.

Justificativa e objetivos: nos anos de 2017 e 2018, Roraima experimentou o aumento mais expressivo nas taxas de incidência sífilis congênita entre todas as unidades federativas. Esse fenômeno ocorreu em paralelo à significativa migração venezuelana para a região. O objetivo do estudo foi analisar a relação entre o aumento dos casos de sífilis congênita registrados no Hospital Materno Infantil Nossa Senhora de Nazareth e a crise migratória venezuelana. Métodos: trata-se de pesquisa de base documental, descritiva, abrangendo os períodos de 2017/2018 e 2020/2021, desenvolvida a partir de dados coletados nas cópias das fichas de notificação/investigação de sífilis congênita do hospital. Resultados: no biênio 2017/2018, ápice da migração venezuelana em Roraima, os casos de sífilis ocorreram em número menor do que quando o fluxo migratório decresceu. No biênio 2020/2021, houve um decréscimo do fluxo migratório em razão do fechamento da fronteira e da aceleração do processo de interiorização. Embora seja o período com o maior registro de notificações de sífilis congênita entre mães venezuelanas, o percentual é consideravelmente menor que o registrado entre mulheres brasileiras. A taxa de incidência foi maior entre o grupo de mães brasileiras (7,5/1.000 nascidos vivos, no período de 2017/2018, e 11,5/1.000 nascidos vivos, no período de 2020/2021). Conclusão: a migração venezuelana, embora possa ter exercido, eventualmente, alguma influência sobre o quantitativo total de casos de sífilis congênita, não pode ser considerada o fator determinante para o aumento de casos da doença no hospital no período delimitado, e outros fatores merecem ser avaliados como decisivos nesse caso.

Abstract Background and Aims Communicating information about the risks and benefits of benzodiazepines so that it is meaningful to the patient has not been previously described. This study aims to determine patient preferences regarding information received before initiating a benzodiazepine. Methods An online survey was distributed through social media and advertisements to Canadians ≥18 years old over a 6‐month period (May–Oct 2022) to collect participant's rating of importance of statements and factors about the risk and benefits of benzodiazepines before initiating treatment using a 10‐point Likert‐type scale. Treatment preferences based on efficacy and risk information were also elicited. The survey was developed and pilot‐tested in collaboration with an advisory committee of individuals with lived and living experience with benzodiazepine use. Results Thirty‐seven participants responded to the survey (mean age 30 years old, 81.1% identified as female). The majority of respondents had a history of anxiety (83.8%) or insomnia (32.4%), and 10 (27.0%) respondents had used a benzodiazepine. Patient counseling related to withdrawal symptoms of benzodiazepines, risk of harm in combination with other sedating agents, risk of physical and psychological dependence, and risk of effects on cognition were rated high in the importance of receiving this information before starting a benzodiazepine relative to efficacy endpoints, such as improvement in sleep parameters. When provided with information about the chance of efficacy and risk of harm, 100% would have selected cognitive behavioral therapy as the best treatment option. The most frequently reported source of medication information where patients have sought information was from the internet (25.0%), followed by doctors (21.9%) and pharmacists (18.8%). Conclusions This study identified patient important factors and statements viewed as important to communicate before initiating a benzodiazepine. The findings of this survey study will help inform decision‐making when considering treatment options for managing anxiety or insomnia.

Introduction Using data in research often requires that the data first be de-identified, particularly in the case of health data, which often include Personal Identifiable Information (PII) and/or Personal Health Identifying Information (PHII). There are established procedures for de-identifying structured data, but de-identifying clinical notes, electronic health records, and other records that include free text data is more complex. Several different ways to achieve this are documented in the literature. This scoping review identifies categories of de-identification methods that can be used for free text data. Methods We adopted an established scoping review methodology to examine review articles published up to May 9, 2022, in Ovid MEDLINE; Ovid Embase; Scopus; the ACM Digital Library; IEEE Explore; and Compendex. Our research question was: What methods are used to de-identify free text data? Two independent reviewers conducted title and abstract screening and full-text article screening using the online review management tool Covidence. Results The initial literature search retrieved 3,312 articles, most of which focused primarily on structured data. Eighteen publications describing methods of de-identification of free text data met the inclusion criteria for our review. The majority of the included articles focused on removing categories of personal health information identified by the Health Insurance Portability and Accountability Act (HIPAA). The de-identification methods they described combined rule-based methods or machine learning with other strategies such as deep learning. Conclusion Our review identifies and categorises de-identification methods for free text data as rule-based methods, machine learning, deep learning and a combination of these and other approaches. Most of the articles we found in our search refer to de-identification methods that target some or all categories of PHII. Our review also highlights how de-identification systems for free text data have evolved over time and points to hybrid approaches as the most promising approach for the future.

Abstract Background To validate case definitions for eczema using primary care Electronic Medical Record (EMR) data from the Canadian Primary Care Sentential Surveillance Network (CPCSSN). Methods This study used EMR data from 1,574 primary care providers in seven Canadian provinces, representing 689,301 patients. Using a subset of patient records seven medical students or family medicine residents created a reference set of 1,772 patients. A total of 23 clinician-informed case definitions were validated against the reference. We assessed agreement using sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV) and overall accuracy. The case definitions with the best agreement statistics were deployed to estimate the prevalence of eczema in the CPCSSN. Results Case definition 1 had the highest SE (92.1%,85.0-96.5) but a lower SP (88.5%,86.7–90.1) and PPV (36.6%,33.1–40.3). Case definition 7 was the most specific case definition with a SP (99.8%, 99.4–100) and PPV (84.2%,61.2–94.7) but low SE (15.8%,9.3–24.5). Case definition 17 had a SE (75.3%, 65.7–83.3), SP (93.8%, 91.5–94.3) and PPV 43.7% (38.3–49.2). When we applied the most specific and most sensitive case definitions, we estimate the prevalence of eczema to be between 0.8 and 15.1%. Case definition 17 suggests an eczema prevalence estimate of 8.2% (8.08–8.21%). Conclusions We validated EMR-based eczema case definitions to estimate the prevalence of clinician-documented eczema. Future studies may choose to apply one or more of these definitions’ dependent on their studies objectives to inform disease surveillance as well as explore burden of illness or interventions related to eczema care in Canada.

Abstract Hypertension is increasing in children and warrants disease surveillance. We therefore sought to evaluate the validity of case definitions to identify pediatric hypertension in administrative healthcare data. Cases of hypertension in children 3–18 years of age were identified utilizing blood pressures recorded in the Manitoba Primary Care Research Network (MaPCReN) electronic medical record from 2014 to 2016. Prevalence of hypertension and associated clinical characteristics were determined. We then evaluated the validity of 18 case definitions combining outpatient physician visits (ICD9CM codes), hospital claims (ICD9CM/ICD10 codes) and antihypertensive use within 1–3 years of data housed at the Manitoba Centre for Health Policy. The MaPCReN database identified 241 children with hypertension and 4090 without (prevalence = 5.6%). The sensitivity of algorithms ranged between 0.18 and 0.51 and the specificity between 0.98 and 1.00. Pharmaceutical use increased the sensitivity of algorithms significantly. The algorithms with the highest sensitivity and area under the ROC curve were 1 or more hospitalization OR 1 or more physician claim OR 1 or more pharmaceutical record. Evaluating 2 years of data is recommended. Administrative data alone reflects diagnosis of hypertension with high specificity, but underestimate the true prevalence of this disease. Alternative data sources are therefore required for disease surveillance.

Abstract Lipids play a central role in platelet physiology. Changes in the lipidome have already been described for basal and activated platelets. However, quantitative lipidomic data of platelet activation, including the released complex lipids, are unavailable. Here we describe an easy-to-use protocol based on flow-injection mass spectrometry for the quantitative analysis of bulk lipid species in basal and activated human platelets and their lipid release after thrombin activation. We provide lipid species concentrations of 12 healthy human donors, including cholesteryl ester (CE), ceramide (Cer), free cholesterol (FC), hexosylceramide (HexCer), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), sphingomyelin (SM) and triglycerides (TG). The assay exhibited good technical repeatability (CVs

The rapid deployment of virtual primary care visits served as a first-line response to COVID-19 and can now be examined for insights, particularly as virtual care is playing an ongoing role in patient care and consultations. Input from primary care providers directly responsible for virtual care delivery is needed to inform policies and strategies for quality care and interactions. The overarching goal of this research study was to examine the use of virtual care as a mechanism for primary healthcare delivery. A phenomenological approach investigated the shift in primary care service delivery as experienced by primary care providers and initiated during the COVID-19 pandemic. Focus groups were conducted with primary care providers (n = 21) recruited through email, advertisements, and professional organizations, exploring how virtual care was delivered, the benefits and challenges, workflow considerations, and recommendations for future use. Integrating virtual care was performed with a great deal of autonomy as well as responsibility, and overwhelmingly depended on the telephone. Technology, communication, and workflow flexibility are three key operational aspects of virtual care and its delivery. Providers highlighted cross-cutting themes related to the dynamics of virtual care including balancing risk for quality care, physician work/life balance, efficiency, and patient benefits. Primary care providers felt that virtual care options allowed increased flexibility to attend to the needs of patients and manage their practice workload, and a few scenarios were shared for when virtual care might be best suited. However, they also recognized the need to balance in-person and virtual visits, which may require guidelines that support navigating various levels of care. Overall, virtual care was considered a good addition to the whole ‘care package’ but continued development and refinement is an expectation for optimizing and sustaining future use.

Introduction and Objectives: The burden of chronic liver disease and cirrhosis continues to increase in North America. We sought to estimate the incidence and prevalence of cirrhosis in Manitoba, Canada over time and assess changes in trends between 2010-2019. Material and Methods: We performed a population-based study using Manitoba administrative health care data, and two validated case-finding algorithms. Annual incidence and prevalence rates were estimated using a generalized linear model with generalized estimating equations, adjusting for age and sex. Changes in estimates were tested using linear trend regression models. Results: Two algorithms estimated the number of prevalent cirrhosis to be 16,140 and 29,943 respectively. The age- and sex-adjusted incidence rates increased over the study (from 149 to 264 cases per 100,000 population in 2010, to 177 to 388 cases per 100,000 population in 2019). Cirrhosis incidence increased annually by 2-6 %, with the largest increase (6-8 % 95 % CI 7-9 %, p

Abstract Experimental trials were conducted to evaluate the effectiveness of mulching with carnauba bagana, a by-product of wax extraction from Copernicia prunifera leaves, on the establishment of 32 shrub and tree species in the Caatinga region. The evaluations were made in areas degraded by mining and embankment of piçarra. Treated plants received 10 L of carnauba mulch in the crown of planted seedlings, while control plants received no mulch. After 24 months, mulching of carnauba improved the growth or survival of eight of the 32 species, while worsening that of two species. Specifically, mulching increased (p