Background: During the COVID-19 pandemic, hygiene behaviors such as keeping distance, avoid-ing masses, wearing face masks and adhering to hand hygiene recommendations became impera-tive. The current study aims to determine factors interrelating with hygiene behaviors. Methods: 4,049 individuals (1,305 male, 2,709 female, aged 18-80 years) were recruited from rehabilitation clinics or freely on the internet and surveyed via online questionnaire between May 2020 and August 2021. Socio-demographics, hygiene behaviors, emotions (fear), life-satisfaction, risk factors and disability as well as communication were assessed. Results: Prevalence for hygiene behaviors was: keeping the distance 84.9%, avoiding mass gatherings 84.6%, wearing face masks 96.5% and hand hygiene 80.7%. Hygiene behaviors were significantly related to fear with linear and quad-ratic associations. Conclusion: Individuals with disabilities, risk factors and psychological symp-toms are more compliant. Especially hand hygiene should be targeted to achieve higher compli-ance rates. A medium level of fear is more functional than too elevated fear. Behavioral interven-tions and targeted communication aiming at improving different behaviors in orchestration can help individuals to remain healthy and maintain a high life-satisfaction. Thereby, communication in the healthcare setting is imperative and all involved individuals should become more aware of this to ensure high hygiene standards and patient safety.

The need for new technologies into healthcare services has been stressed. However, little is known about the effectiveness of digital interventions integrated in psychosomatic rehabilitation processes. Data from 724 patients from psychosomatic rehabilitation clinics were analyzed for effectiveness of digital trainings examined by a change in symptoms related to depression, anxiety, stress and loneliness from pre- to post-rehabilitation. Rehabilitation satisfaction was examined in association with reaching rehabilitation goals and satisfaction with communication. Mixed repeated measures analysis of covariances, analysis of covariances, and hierarchical stepwise regression analyses were performed. Results indicated a superior effectiveness for the intervention group receiving all offered digital treatments in addition to the regular face-to-face rehabilitation program with regard to symptoms of depression, F(2,674)=3.93, p<.05, ηp2=.01), and anxiety, F(2,678)=3.68, p<.05, ηp2=.01), post-rehabilitation with large effect sizes for both depression (d=1.28) and anxiety (d=1.08). In addition, rehabilitation satisfaction was positively associated with reaching rehabilitation goals and perceived communication with healthcare workers. Digital interventions appeared effective in supporting mental health of psychosomatic rehabilitation patients post-rehabilitation. This finding supports the inclusion of multidisciplinary and interdisciplinary digital and face-to-face treatment programs and call for more implementations of new technologies in a context of complexity to improve health and healthcare service.

(1) Background: Obstetric work requires good communication, which can be trained in interventions targeting health care providers and pregnant women/ patients. This systematic review aims to aggregate the current state of research on communication interventions in obstetrics. (2) Methods: Using the PICOS scheme, studies published in peer-reviewed journals in English or German between 2000 and 2020 were searched. Out of 7,018 results, 71 studies were included in this synthesis and evaluated using the Oxford Level of Evidence Scale. (3) Results: 63 studies, including a communication component, revealed a positive effect on different proximal outcomes (i.e., communication skills). Three studies evaluating the effect of communication training on distal performance indicators (i.e., patient safety) proved to be beneficial to some extent. Most studies included different groups at the same time; those addressing health care providers were more common than those with students (61 vs. 12). Expectant mothers were targeted only in 9 studies. Overall, the evidence level of studies was low (only 11 RCTs), with 24 studies evidence level of I-II, 35 of III, and 10 of IV. (4) Conclusions: Communication training should be applied more often to improve communication of staff, students, and pregnant women, and thereby improve patient safety.

Sterol homeostasis in mammalian cells and tissues involves balancing three fundamental processes: de novo sterol biosynthesis; sterol import (e.g., from blood-borne lipoproteins); and sterol export. In complex tissues, composed of multiple different cell types (such as the retina), import and export also may involve intra-tissue, inter-cellular sterol exchange. Disruption of any of these processes can result in pathologies that impact the normal structure and function of the retina. Here, we provide a brief overview of what is known currently about sterol homeostasis in the vertebrate retina and offer a proposed path for future experimental work to further our understanding of these processes, with relevance to the development of novel therapeutic interventions for human diseases involving defective sterol homeostasis.

Research is still lacking regarding the question as to how programs to promote healthy aging should be organized in order to increase acceptance and thus effectiveness. For older adults, ecological factors, such as physical distance to program sites, might predict participation and retention. Thus, the key aim of this analysis was to examine these factors in a physical activity intervention trial. Adults (N=8,299) aged 65 to 75 years were invited to participate and n=589 participants were randomly assigned to one of two intervention groups with 10 weeks of physical activity home practice and exercise classes or a wait-list control group. Response, participation, and dropout data were compared regarding ecological, individual, and study-related variables. Kaplan-Meier curves and Cox regression models were used to determine predictors of dropout. In total, 405 participants completed the study. Weekly class attendance rates were examined regarding significant weather conditions and holiday periods. The highest rates of nonresponse were observed in districts with very high neighborhood levels of socioeconomic status. In this study, ecological factors did not appear to be significant predictors of dropout, whereas certain individual and study-related variables were predictive. Future studies should consider these factors during program planning to mobilize and keep subjects in the program.

The move from paper to online is not only necessary for remote working, it is also significantly more sustainable. This trend has seen a rising need for high-quality digitization of content from pages and whiteboards to sharable online material. But capturing this information is not always easy, nor are the results always satisfactory. Available scanning apps vary in their usability and do not always produce clean results, retaining surface imperfections from the page or whiteboard in their output images. CleanPage, a novel smartphone-based document and whiteboard scanning system, is presented. CleanPage requires one button-tap to capture, identify, crop and clean an image of a page or whiteboard. Unlike equivalent systems, no user intervention is required during processing and the result is a high-contrast, low-noise image with a clean homogenous background. Results are presented for a selection of scenarios showing the versatility of the design. CleanPage is compared with two market leader scanning apps using two testing approaches: real paper scans and ground-truth comparisons. These comparisons are achieved by a new testing methodology that allows scans to be compared to unscanned counterparts, by using synthesized images. Real paper scans are tested using image quality measures. An evaluation of standard image quality assessments is included in this work and a novel quality measure for scanned images is proposed and validated. The user experience for each scanning app is assessed, showing CleanPage to be fast and easier to use.

In this paper we propose the generation of synthetic small and more sophisticated molecule structures that optimize the binding affinity to a target (ASYNT-GAN). To achieve this we leverage on three important achievements in A.I.: Attention, Deep Learning on Graphs and Generative Adversarial Networks. Similar to text generation based on parts of text we are able to generate a molecule architecture based on an existing target. By adopting this approach, we propose a novel way of searching for existing compounds that are suitable candidates. Similar to question and answer Natural Language solutions we are able to find drugs with highest relevance to a target. We are able to identify substructures of the molecular structure that are the most suitable for binding. In addition, we are proposing a novel way of generating the molecule in 3D space in such a way that the binding is optimized. We show that we are able to generate compound structures and protein structures that are optimised for binding to a target.

Due to the continuing high suicide rates among young men, there is a need to understand help-seeking behaviour and engagement with tailored suicide prevention interventions. The aim of this study was to compare help-seeking among younger and older men who attended a therapeutic centre for men in a suicidal crisis. In this case series study, data were collected from 546 men who were referred into a community-based therapeutic service in North West England. Of the 546 men, 337 (52%) received therapy; 161 (48%) were aged between 18 and 30 years (mean age 24 years, SD=3.4). Analyses included baseline differences, symptom trajectories for the CORE-34 Clinical Outcome Measure (CORE-OM) and engagement with the therapy. For the CORE-OM there was a clinically significant reduction in mean scores between assessment and discharge (p<0.001) for both younger and older men. At initial assessment, younger men were less affected by entrapment (46% v 62%; p=.02), defeat (33% v 52%; p=.01), not engaging in new goals (38% v 47%; p=.02), and positive attitudes towards suicide (14% v 18%; p=.001) than older men. At discharge assessment, older men were significantly more likely to have an absence of positive future thinking (15% v 8%; p=0.03), have less social support (45% v 33%; p=.02) and feelings of entrapment (17% v 14%; p=.02) than younger men. Future research needs to assess the long-term effects of help-seeking using a brief psychological intervention for young men in order to understand whether the effects of the therapy are sustainable over a period of time following discharge from the service.

Leadership and sustainability have been researched and examined concurrently. We know much about sustainable, sustainability and environmental leadership as separate areas of research and the leadership behaviours and practices that facilitate achievement of sustainability outcomes. Whilst these research streams have developed alongside each other, we know little about the similarities and differences of each of these three leadership approaches. The purpose of this paper is to review and compare which sustainable, sustainability and environmental leadership approaches are predictive of improved organizational performance with a view to understanding leadership towards sustainability. Through a comprehensive review of the extant literature, we integrate the three leadership approaches and highlight areas of similarity and difference. From a theoretical perspective, this paper seeks to make a significant contribution to the scholarly literature by building on current knowledge and developing a unified framework that combines our findings on leadership practices and behaviours in terms of the types of leadership required for achieving sustainability outcomes. By unifying existing frameworks and clarifying points of integration and differentiation under the umbrella of ‘leadership towards sustainability’, this paper seeks to advance research on leadership approaches. From a practical perspective, a cohesive set of leadership behaviours and practices will be emphasized so that leaders can adapt these to suit the context of their organization, thus helping leaders make sense of the literature to inform their practice and reach sustainability goals. Thus, the main goal of this paper is to identify a range of leadership behaviours and practices that are required to improve the performance of sustainability in organizations thus informing the broader leadership field.

Due to the continuing high suicide rates among young men, there is a need to understand help-seeking behaviour and engagement with tailored suicide prevention interventions. The aim of this study was to explore help-seeking behaviour and engagement for young men aged 18 to 30 years who attended a therapeutic centre for men in a suicidal crisis. In this prospective cohort study, data were collected from 546 men who were referred into a community-based therapeutic service in North West England. Of the 546 men, 337 (52%) received therapy; 161 (48%) were aged between 18 and 30 years (mean age 24 years, SD=3.4). One third (n=54; 34%) of the men were seen within 48 hours of their referral. Analyses included baseline differences, symptom trajectories for the CORE-34 Clinical Outcome Measure (CORE-OM) and engagement with the therapy. For the CORE 34 there was a clinically significant reduction in mean scores between assessment and discharge (p<0.001), with all outcomes demonstrating a large effect size. Future research needs to assess the long-term effects of help-seeking using a brief psychological intervention for young men in order to understand whether the effects of the therapy are sustainable over a period of time following discharge from the service.

Urban vitality, understood as a key factor for the achievement of cities’ sustainability, shows a strong relationship with urban morphology. The city theorist Jane Jacobs suggested morphologi-cal aspects to promote vital cities already in the 1960s, which remain valid in the present. How-ever, few studies in the Andean region quantitatively exemplify this. This paper aims to test the measurement of urban vitality in a neighborhood of Quito, Ecuador, called La Mariscal, inte-grating Jacobs’ approach. In particular, three urban vitality indexes are evaluated with the appli-cation of GIS software using cadastral data obtained from the municipality and field data col-lection. Results show that the context-based previous knowledge and the scale of analysis are es-sential factors in the configuration of dimensions, indicators, and spatial representation of any urban vitality index. In the study area land use mixture, contact opportunity, and accessibility dimensions are fundamental. Regarding indicators, the incorporation of the informal small-scale commerce, the quality of sidewalks, the street slope, and the good-conditioned street furniture is recommended. Finally, a hybrid representation (raster and vectorial) is suggested to precisely measure urban vitality at a block scale. Altogether, by providing a comparative approach, we in-tend to bring a useful framework for researchers and planners to study urban vitality in Andean cities.

A selection of 36 commercial probiotic fermented dairy products from UK and Europe markets were evaluated for the numbers, types and viability of Lactobacillus strains against the stated information on their packages. A comparative study was carried out on selectivity of MRS-Clindamycin, MRS-Sorbitol and MRS-IM Maltose, to select the right medium for enumeration of probiotic Lactobacillus. Based on selectivity of medium for recovery of the targeted lactobacilli and also simplicity of preparation, MRS-Clindamycin was chosen as the best medium for enumeration of probiotic Lactobacillus in fermented milks. The results of enumeration of lactobacilli showed that 22 out of a total 36 tested products contained more than 106 colony forming units/g at the end of their shelf- life, which comply with the recommended minimum therapeutic level for probiotics. Rep-PCR using primer GTG-5 was applied for initial discrimination of isolated strains, and isolates, which presented different band profile, were placed in different groups. The isolated Lactobacillus spp. were identified mainly as Lactobacillus acidophilus, Lactobacillus casei and Lactobacillus paracasei by analysis of partial sequences of the 16S ribosomal RNA and rpoA genes. In conclusion, it is unknown to recommend the adequate number of probiotic bacteria to be consumed to ensure the beneficial properties.

For Visually impaired People (VIPs), the ability to convert text to sound can mean a new level of independence or the simple joy of a good book. With significant advances in Optical Character Recognition (OCR) in recent years, a number of reading aids are appearing on the market. These reading aids convert images captured by a camera to text which can then be read aloud. However, all of these reading aids suffer from a key issue – the user must be able to visually target the text and capture an image of sufficient quality for the OCR algorithm to function – no small task for VIPs. In this work, a Sound-Emitting Document Image Quality Assessment metric (SEDIQA) is proposed which allows the user to hear the quality of the text image and automatically captures the best image for OCR accuracy. This work also includes testing of OCR performance against image degradations, to identify the most significant contributors to accuracy reduction. The proposed No-Reference Image Quality Assessor (NR-IQA) is validated alongside established NR-IQAs and this work includes insights into the performance of these NR-IQAs on document images.

There is a disproportionate increase in the incidence of diet-related cardiometabolic disorders in racial and ethnic minority groups. This systematic review examines the extent to which diet-induced changes in health outcomes have been discussed by race or ethnicity in randomized controlled trials recruiting both minority and non-Hispanic White groups. Databases i.e. PubMed, Cochrane library and Web of Science were searched up to November 2019. Studies that discussed effects of defined dietary interventions on health outcomes by racial or ethnic minority group vs. non-Hispanic Whites (n=29) were included in the review. Most studies were conducted in Black vs. White people testing effects of energy restriction, macronutrient modification, sodium reduction, or variations of the Dietary Approaches to Stop Hypertension (DASH) diet on cardiometabolic outcomes. There was limited focus on other minority groups. Evidence suggests greater blood pressure reduction for Black people compared to Whites particularly on DASH (or similar) diets. Overall, there was limited consideration for group-specific eating patterns and diet acceptability in most studies. Adequately powered studies are needed for accurate interpretation of race by diet effects. With emerging precision nutrition initiatives, it is imperative to ensure adequate representation of racial and ethnic subgroups for addressing nutrition-related health disparities.

In 1789, the Annonaceae family was cataloged by de Jussieu. It encompasses tropical and subtropical plants which are widespread in distribution across various continents such as Asia, South and Central America, Australia and Africa. The genus of Annona is one of the 120 genera of the Annonaceae family and contains more than 119 species of trees and shrubs. The majority of these species are found in tropical America with more than 105 species (26 of them are endemic). Due to its edible fruits and medicinal properties, Annona is the most important genus of Annonaceae family. Despite Annona having many species, only limited species of this family are economically important such as A. squamosa L. (sugar apple), A. cherimola Mill. (Cherimoya), A. muricata L. (guanabana or soursop), A. atemoya Mabb. (atemoya), a hybrid between A. cherimola and A. squamosa, A. reticulata L. (custard apple), A. glabra L. (pond-apple) and A. macroprophyllata Donn. Sm. (ilama). Phytochemically, several classes of secondary metabolites such as acetogenins, essential oils, alkaloids, terpenoids and flavonoids have been described in this genus. A variety of pharmacological activities have been reported from various parts of Annona species specially leaves and seeds including applications against antibacterial, anticancer, antidiabetic and anti-inflammatory.

According to Hofstede’s theory of cultural dimensions, cultures differ in cultural values and norms; values and norms that may influence differences in trendsetting, creative traits and behaviors, and pro-environmental behaviors. Further, because men and women have been socialized within particular cultures, gender differences may exist in trendsetting, creative traits and behaviors, and pro-environmental behaviors. Trendsetters have characteristics that are interrelated with creative traits and behaviors, perhaps inclining them to endorse pro-environmental behaviors. However, the interrelationships among these variables remain unexplored. Thus, the purpose of this study was to examine these three variables among college students in South Korea and the United States, specifically looking at cultural and gender differences. Participants were 225 Korean college students and 221 U.S. college students. Questionnaires included demographic items and scales measuring trendsetting, creative traits and behaviors, and pro-environmental behaviors. Data analyses included descriptive statistics, Cronbach’s alpha reliability, MANOVA, ANOVA and SNK posthoc test. Results show that U.S. (vs Korean) students indicated greater trendsetting and creative traits and behaviors but not greater pro-environmental behaviors. Fashion trendsetting groups in both Korea and the U.S. differed in creative traits and behaviors and pro-environmental behaviors. Among Korean trendsetting groups, reluctant adopters scored lowest on creative traits and behaviors and pro-environmental behaviors. Among U.S. trendsetting groups, trendsetters scored highest on creative traits and behaviors and pro-environmental behaviors; reluctant adopters scored lowest on pro-environmental behaviors. Theoretical and practical implications are provided for researchers and marketers.

COVID-19 is the most severe health crisis of the 21st century. COVID-19 presents a threat to almost all countries world-wide. The restriction of human mobility is one of the strategies used to control the transmission of COVID-19. However, it has yet to be determined how effective this restriction is in controlling the rise in COVID-19 cases, particularly in major capital cities such as Jakarta, Indonesia. Using Facebook's mobility data, our study explores the impact of restricting human mobility on COVID-19 case control in Jakarta. Our main contribution is showing how the restriction of human mobility data can give important information about how COVID-19 spreads in different places. We proposed modifying a global regression model into a local regression model by accounting for the spatial and temporal interdependence of COVID-19 transmission across space and time. We applied Bayesian hierarchical Poisson spatiotemporal models with spatially varying regression coefficients. We estimated the regression parameters using an Integrated Nested Laplace Approximation. We found that the local regression model with spatially varying regression coefficients outperforms the global regression model based on DIC, WAIC, MPL, and R2 criteria for model selection. In Jakarta's 44 districts, the impact of human mobility varies significantly. The impacts of human mobility on the log relative risk of COVID-19 range from –4.445 to 2.353. The prevention strategy involving the restriction of human mobility may be beneficial in some districts but ineffective in others. Therefore, a cost-effective strategy had to be adopted.

Although fragility fractures, osteoporosis, sarcopenia and frailty are becoming more prevalent in our aging society the treatment options are limited and preventative strategies are needed. Despite magnesium being integral bone and muscle physiology the relationship between dietary magnesium and skeletal muscle and bone health has not been investigated concurrently before. We analysed cross-sectional associations between dietary magnesium and skeletal muscle mass (as fat free mass – FFM), grip strength and bone density (BMD) in 156,575 men and women aged 39-72 years from the UK Biobank cohort. FFM was measured with bioelectrical impedance and expressed as the percentage of body weight (FFM%) or divided by body mass index (FFM_BMI). Adjusted mean grip strength, FFM%, FFM_BMI, and BMD were calculated according quintiles of dietary magnesium, correcting for covariates. Significant inter-quintile differences across intakes of magnesium existed in men and women respectively of 1.1% and 2.4% for grip strength, 3.0% and 3.6% for FFM%, 5.1% and 5.5% for FFM_BMI, and 2.9% and 0.9% for BMD. These associations are as great or greater than annual measured losses of these musculoskeletal outcomes indicating potential clinical significance. Our study suggests that dietary magnesium may play a role in musculoskeletal health and have relevance for population prevention strategies for sarcopenia, osteoporosis and fractures.

Probiotics have been used to ameliorate gastrointestinal symptoms since ancient times. Over the past 40 years, probiotics have been shown to exert major effects on the immune system, both in vivo and in vitro. This interaction is clearly linked to gut microbes, their polysaccharide antigens, and key metabolites produced by these bacteria. At least four metabolic pathways have been implicated in mechanistic studies of probiotics, based on carefully studied animal models. Microbial-immune system crosstalk has been linked to short chain fatty acid production and signaling, tryptophan metabolism and the activation of aryl hydrocarbon receptors, nucleoside signaling in the gut, and activation of the intestinal histamine-2 receptor. Several randomized controlled trials have now shown that microbial modification by probiotics may improve gastrointestinal symptoms and multi-organ inflammation in rheumatoid arthritis, ulcerative colitis, and multiple sclerosis. Future work will need to carefully assess safety issues, selection of optimal strains and combinations, and attempts to prolong the duration of colonization of beneficial microbes.

The root extracts of Symphytum officinale (comfrey) are commonly used in traditional medicine to treat muscle, joint, skin and bone disorders. However, little information is available on the biomedical functions of comfrey leaves. In this study, sequencing results of Internal Transcribed Spacer and trnL-trnF genes showed that plants purchased from the local market were comfrey and named as S. officinale WL (WL). The optimal extraction conditions of WL leave with the highest extract yield and contents of total phenols and flavonoids by microwave-assisted extraction were identified. The antioxidative and anti-inflammatory activities and possible molecular mechanism(s) of the WL leaf extract (WLE) were evaluated. Furthermore, the major component of WLE was identified as rosmarinic acid by HPLC. Results showed that the optimal extract condition was obtained with 750W microwave power, 50℃, 75% methanol, the solid-to-solvent ratio of 1:10, and 15 minutes. Results of all DPPH, ABTS and superoxide radical scavenging activities, reducing power, ferrous ion chelating activity, and ferric reducing antioxidant power showed high antioxidative capacities of WLE. Furthermore, WLE showed obvious DNA protecting activity. WLE attenuated lipopolysaccharides-stimulated inflammation by suppressing iNOS, COX-2, IL-1β, IL-6, and TNF-α expressions in RAW264.7 macrophages. These attenuations involved in inactivations of lipopolysaccharides-induced NF-κB and MAPK signaling pathways.

Assistance dogs provide significant benefits to older adult owners. However, despite protective legislation, aged care facilities continue to not allow owners to retain their dog on relocation. The purpose of the current study was to explore whether older adults should be allowed to retain their dog on relocation to an aged care facility, and what factors should impact this decision. Further, if allowed to retain their dog, what would be the best practice to allow for this. A deliberative democracy methodology was used, with a range of key stakeholders recruited. Focus groups were held, with follow up questionnaire to establish deliberation for all questions. Results indicated that with sufficient objective measurement, fair decisions can be made to ensure the welfare and wellbeing for owner and dog. Key policy and procedure changes would also be necessary to ensure ongoing support, such as training, care plans, and emergency directives. By ensuring sufficient policies and procedures are in place, training and support could lead to an ideal outcome where facilities could be at the forefront of a better future for aged care.

Management of Sclerotinia stem rot (SSR) disease in Brassica napus is heavily reliant on prophylactic fungicide applications at flowering, which often provides inconsistent control depending on timing of ascospore release in the field and environmental conditions. Understanding host response to Sclerotinia sclerotiorum infection is essential for sustainable disease management in the future. This study determined the host response of nine B. napus varieties to four aggressive S. sclerotiorum isolates across two years by measuring four disease variables; area under the disease progress stairs (AUDPS), seed production, sclerotia number and average sclerotia weight. Brassica napus varieties varied greatly in their response to the four measured variables, with varieties producing the highest AUDPS not the same varieties that had the lowest seed production, the highest numbers of sclerotia or heaviest sclerotia. Repeating the experiment over two years using the same varieties and isolates identified the impact of environment as the most influential factor on measured disease variables, highlighting the complexity of disease responses to diverse isolates and host genotypes under different environments. It was recommended that both long-term (such as inoculum production) and short-term (such as seed production) disease outcomes be combined with lesion length measurement (i.e. AUDPS) for future host screening studies.

To increase the power density of the electromechanical drive train of wind turbines, journal bearings can be used as planetary gear bearings instead of rolling bearings. This technological change presents new challenges. For example, wind turbine drive systems are subject to dynamic and low-speed operating conditions which can lead to an accelerated abrasive wear of the journal bearings. In addition, oil supply failure or peak loads due to wind gusts and grid and power converter faults could potentially result in catastrophic failure due to adhesive wear in a very short time. Such operating characteristics are, therefore, critical regarding the journal bearing wear lifetime and must be considered in the design. The successful implementation of journal bearings in wind turbines depends on a reliable estimation of adhesive and abrasive wear. In this paper, five different models for the wear calculation of journal bearings are evaluated regarding their suitability of wear calculation of planetary gear bearings in wind turbines. For this purpose, the following evaluation criteria were defined: parameter uncertainty, parametrization effort, in particular number of parameters, parameterization method and load case dependency of parameters and calculation effort. In order to be able to evaluate the wear models, the wear models are numerically implemented and the wear of a test journal bearing is exemplarily calculated under load conditions, which are comparable to load conditions in a wind turbine. Relevant influences from the wind turbine system such as lubricant, material and manufacturing dependent surface influences like roughness and hardness are considered. The wear models are evaluated with respect to their fulfillment of the defined criteria. The resulting evaluation allows the selection of a wear model that can be used to calculate the wear of planetary gear journal bearings in wind turbines, considering the available input variables.

The use of small Unmanned Aircraft Systems (sUAS ) as platforms for data capture has rapidly increased in recent years. However, while there has been significant investment in improving the aircraft, sensors, operations, and legislation infrastructure for such, little attention has been paid to supporting the management of the complex data capture pipeline sUAS involve. This paper reports on the outcomes of a four-year-long community-engagement-based investigation into what tools, practices, and challenges currently exist for particularly researchers using sUAS as data capture platforms. The key results of this effort are: (1) sUAS captured data – as a set that is rapidly growing to include data in a wide range of Physical and Environmental Sciences, Engineering Disciplines, and many civil and commercial use cases – is characterised as both sharing many traits with traditional remote sensing data and also as exhibiting – as common across the spectrum of disciplines and use cases – novel characteristics that require novel data support infrastructure. And (2), given this characterization of sUAS data and its potential value in the identified wide variety of use case, we outline eight challenges that need to be addressed in order for the full value of sUAS captured data to be realized. We then conclude that there would be significant value gained and costs saved across both commercial and academic sectors if the global sUAS user and data management communities were to address these challenges in the immediate to near future, so as to extract the maximal value of sUAS captured data for the lowest long-term effort and monetary cost.

This paper presents the Advanced Syntactic-Graph Convolutional Model (ASGCM), a pioneering approach in Aspect-Based Sentiment Analysis (ABSA) that integrates syntactic dependency features within a graph convolution framework. ASGCM stands out for its novel use of dependency edge encoding and tag-based graph convolutions, providing a fine-grained analysis of sentiments associated with specific aspects in text. This model meticulously captures the intricacies of syntactic structures, thereby offering enhanced precision in sentiment analysis. Notably, ASGCM incorporates a dual-layer graph convolution system: one layer processes syntactic dependencies (edges), while the other interprets semantic roles (tags), ensuring a comprehensive understanding of both structural and contextual elements in text. We rigorously tested ASGCM on multiple datasets, including both English and Chinese languages, and our findings reveal a significant improvement in sentiment classification accuracy compared to existing models. The versatility of ASGCM makes it a robust tool for diverse linguistic environments, setting a new standard for ABSA methodologies.

As our understanding of the thalamocortical system deepens, the questions we face become more complex. Their investigation requires the adoption of novel experimental approaches complemented with increasingly sophisticated computational modeling. In this review, we take stock of current data and knowledge about the circuitry of the somatosensory thalamocortical loop in rodents, discussing common principles across modalities and species whenever appropriate. We review the different levels of organization, including the cells, synapses, neuroanatomy, and network connectivity. We provide a complete overview of this system that should be accessible for newcomers to this field while nevertheless being comprehensive enough to serve as a reference for seasoned neuroscientists and computational modelers studying the thalamocortical system. We further highlight key gaps in data and knowledge that constitute pressing targets for future experimental work. Filling these gaps would provide invaluable information for systematically unveiling how this system supports behavioral and cognitive processes.

Next-generation sequencing (NGS) has actualized human papillomavirus (HPV) virome profiling for in-depth investigation of viral evolution and pathogenesis. However, viral computational analysis remains a bottleneck due to semantic discrepancies between computational tools and curated reference genomes. To address this, we developed and tested automated workflows for HPV taxonomic profiling and visualization using a customized Papillomavirus database in CLC Microbial Genomics Module. HPV genomes from Papilloma Virus Episteme were customized and incorporated into CLC “ready-to-use” workflows for stepwise data processing to include: 1) Taxonomic Analysis, 2) Estimate Alpha/Beta Diversities, and 3) Map Reads to Reference. Low-grade (n = 95) and high-grade (n = 60) Pap smears were tested with ensuing collective runtimes: Taxonomic Analysis (36 min); Alpha/Beta Diversities (5 sec); Map Reads (45 min). Tabular output conversion to visualizations entailed 1-2 keystrokes. Biodiversity analysis between low- (LSIL) and high-grade squamous intraepithelial lesions (HSIL) revealed loss of species richness and gain of dominance by HPV-16 in HSIL. Integrating clinically relevant, taxonomized HPV reference genomes within automated workflows proved to be an ultra-fast method of virome profiling. The entire process named “HPV DeepSeq” provides a simple, accurate and practical means of NGS data analysis for a broad range of applications in viral research.

New coronavirus (SARS-CoV-2) treatments and vaccines are under development to combat the COVID-19 disease. Several approaches are being used by scientists for investigation including 1) various small molecule approaches targeting RNA polymerase, 3C-like protease, and RNA endonuclease and 2) exploration of antibodies obtained from convalescent plasma from patients who have recovered from COVID-19. The coronavirus genome is highly prone to mutations that lead to genetic drift and escape from immune recognition; thus, it is imperative that sub-strains with different mutations are also accounted for during vaccine development. As the disease has grown to become a pandemic, new B-cell and T-cell epitopes predicted from SARS coronavirus have been reported. Using the epitope information along with variants of the virus, we have found several variants which might cause drifts. Among such variants, 23403A>G variant (p.D614G) in spike protein B-cell epitope is observed frequently in European countries such as the Netherlands, Switzerland and France.

The process of viral integration into the host genome is an essential step of the HIV-1 life cycle. The viral Integrase (IN) enzyme catalyses integration. IN is an ideal therapeutic enzyme targeted by several drugs; raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG) and bictegravir (BIC) having been approved by the USA Food and Drug Administration (FDA). Due to high HIV-1 diversity, it is not well understood how specific naturally occurring polymorphisms (NOPs) in IN may affect the structure/function and binding affinity of Integrase Strand Transfer Inhibitors (INSTIs). In this study, we applied computational methods of molecular modelling and docking to analyse the effect of NOPs on the full-length IN structure and INSTI binding. We identified 16 NOPs within the Cameroonian derived CRF02_AG IN sequences and further identified 17 NOPs within HIV-1C South African sequences. The NOPs in the IN structures did not show any effect on INSTI binding. INSTIs displayed similar binding affinities to each IN structure. All INSTIs are clinically effective against diverse HIV-1 strains from INSTI treatment naïve populations. This study supports the use of second-generation INSTI DTG as part of first-line combination antiretroviral therapy (cART) regimens, due to DTG possessing a stronger genetic barrier to the emergence of drug resistance.

Personalized treatment based on driver molecular alterations, such as ALK rearrangement, has revolutionized the therapeutic management of advanced oncogene addicted NSCLC patients. Multiple effective ALK tyrosine kinase inhibitors (TKIs), with the amelioration of the activity at central nervous system level, are now available, leading to substantial prognosis improvement. The exposure to TKIs triggers resistance mechanisms and the sequential administration of other TKIs and chemotherapy is, for the most part, not targeted. In this context, extending the benefit deriving from precision medicine is paramount, above all when disease progression occurs in a limited number of sites. Retrospective data indicate that, in oligoprogressive disease, targeted therapy beyond progression combined with definitive local treatment of the progressing site(s) is an effective alternative. In these cases, multidisciplinary approach becomes essential for an integrated treatment strategy, depending on the site of disease progression, in order to improve not only survival, but also quality of life. In this review we provide an updated and comprehensive overview of the main treatment strategies in case of ALK rearranged oligoprogression, including systemic treatment as well as local therapy, and report real-world clinical stories, with the final aim of identifying the most promising management for this subset of patients.

Phytopathogenic oomycetes are known to infect a host plant successfully due to their ability to secrete a set of protein effectors. Of interest to many researchers are effectors with the N-terminal RxLR motif (Arginine-any amino acid-Leucine-Arginine). Owing to the genome sequencing, we can now comprehend the high level of diversity among oomycete effectors, and similarly, their conservation within and among species core RxLR effectors (CREs). Currently, there are a couple of putative CREs that have been identified in oomycetes. The functional characterization of these CREs proposes their virulence role with the potential of targeting central cellular processes that are conserved across diverse plant species. This could be harnessed in engineering plants for broad-spectrum and durable resistance.

1) Public health remains a tiny portion of the undergraduate pharmacy curriculum and the material is integrated into other modules. The objective of this study is to describe the UK undergraduate pharmacy curriculum, including its public health content; 2) Methods: A qualitative method (content analysis of websites) was used to describe the UK undergraduate pharmacy curriculum and teaching and learning policy. This involved selecting relevant concepts and then quantifying their presence and the relationships between them. The NVivo software was used to carry out ‘group queries’ and visualisation of results; 3) Results: Public health remains an optional module in the curricula of many UK schools of pharmacy. Several public health-related topics are often integrated into other modules, but UK undergraduate pharmacy curricula are still dominated by traditional pharmacy modules; and 4) Conclusions: Most of the curricula analysed were dominated by traditional pharmacy modules designed to enhance students' knowledge and skills. The skill set of UK pharmacy students with respect to macro-level public health activities needs to be improved in order to enhance pharmacists’ contribution to public health.

PTK6, a Non-Receptor–Tyrosine-Kinase, modulates the pathogenesis of breast and prostate cancers, and is recognized as a biomarker of breast cancer prognosis. There are over 30 known substrates of PTK6, including signal transducers, transcription factors and RNA binding proteins. Many of these substrates are known drivers of other cancer types such as colorectal cancer. Colon and rectal tumours also express higher levels of PTK6 than the normal intestine suggesting a potential role in tumorigenesis. However, the importance of PTK6 in colorectal cancer remains unclear. PTK6 inhibitors such as XMU-MP-2 and Tilfrinib have demonstrated potency and selectivity in breast cancer cells when used in combination with chemotherapy, indicating the potential for PTK6 targeted therapy in cancer. However, most of these inhibitors are yet to be tested in other cancer types. Here, we discuss the current understanding of the function of PTK6 in normal intestinal cells compared with colorectal cancer cells. We review existing PTK6 targeting therapeutics and explore the possibility of PTK6 inhibitory therapy for colorectal cancer.

Immune responses to influenza (flu) antigens reflect memory to prior infections or vaccinations, which might influence immunity to new flu antigens. Memory of past antigens has been termed “original antigenic sin” or more recently “immune imprinting” and “seniority”. We have researched a comparison between the immune response to live flu infections and inactivated flu vaccina-tions. A brief history of antibody generation theories is presented culminating in new findings about the immune-network theory suggesting that a network of clones exists between an-ti-idiotypic antibodies and T cell receptors. Findings regarding the 2009 pandemic flu strain and immune responses to it are presented, including memory B cells and conserved regions within the hemagglutinin protein. The importance of CD4+ memory T cells and cytotoxic CD8+ T cells responding to both infections and vaccinations are discussed and compared. Innate immune cells like natural killer (NK) cells and macrophages are discussed regarding their roles in adaptive immune responses. Antigen presentation via macroautophagy processes are described. New vaccines in development are mentioned along with the results of some clinical trials. The manu-script concludes with how repeated vaccinations are impacting the immune system and a sketch of what might be behind the imprinting phenomenon, including future research directions.

The field of mitochondrial genomics has advanced rapidly and revolutionized disciplines from molecular anthropology, population genetics, to medical/oncogenetics. However, mtDNA next-generation sequencing (NGS) analysis for matrilineal haplotyping and phylogeographic inference remains hindered by the lack of a consolidated, mitogenome database and efficient bioinformatics pipeline. To address this, we developed a customized human mitogenome database (hMITO DB) embedded in a CLC Genomics workflow for read mapping, variant analysis, haplotyping, and geo-mapping. The database was constructed from 4,286 mitogenomes. The macro-haplogroup (A to Z) distribution and representative phylogenetic tree were found consistent with published literature. The hMITO DB automated workflow was tested using mtDNA-NGS sequences derived from Pap smears and cervical cancer cell lines. The auto-generated read mapping, variants track, and table of haplotypes and geo-origins were completed in 15 min for 47 samples. The mtDNA workflow proved to be a rapid, efficient and accurate means of sequence analysis for translational mitogenomics.

(1) Background: Prevention of acute cardiovascular events in patients with cardiovascular diseases (CVDs) requires promoting health-protective behaviors (e.g., physical activity) and preventing health-compromising behaviors (sitting). Digital health interventions provide much potential. Based on multiple behavioral change theory, an intervention (reCardial app) was evaluated, and the following hypotheses were tested: H1: Health behaviors (physical activity, sitting) and disease self-management (self-care maintenance, self-care confidence) are closely interrelated. H2: Change in health behaviors and disease self-management indicators over time is more pronounced in reCardial app-users. H3: In the intervention group, changes in systolic and diastolic blood pressure indicate a positive trajectory. (2) Methods: A study with the design of a randomized controlled trial over 12 weeks was conducted. 40 CVD-patients were randomized equally to the Intervention Group (35% women; Mage=60.6years) and Control Group (45% women; Mage=61.5years). (3) Results: Findings support H1 with significant correlations between health behaviors (r=0.45-0.63**), and disease self-management (r=-0.32-0.54**), H2 with Eta²=0.21 (not statistically significant) and H3 partially with d=0.101 for systolic blood pressure but not regarding diastolic blood pressure. (4) Conclusions: Replications are needed with larger samples and more objective measures. The app can help prevent and manage CVD by means of promoting health-protective behaviors and preventing health-compromising behaviors. Taking different behaviors into account can increase intervention effects and with that support of users.

This experiment examined the effect of feeding graded levels of Momordica foetida leaf (MFL) as a substitute for Noug Seed Cake (NSC) on feed intake, digestibility, growth performance, and economic efficiency. Forty-two yearling lambs (16.1±0.6 kg) were randomly allotted to six dietary treatment groups for 90 days feeding trial followed by ten days digestibility trial. Treatments were T1(Control) = adlibitum PG (Pennisetum glaucifolium) + 449.3gm WB (Wheat Bran), T2 = 449.3gm WB + 100% MFL; T3 = 449.3gm WB + 75% MFL + 25% NSC; T4 = 449.3gm WB + 50% MFL + 50% NSC; T5 = 449.3gm WB + 25% MFL + 75% NSC; T6 = PG + 449.3gm WB + 0% MFL + 100% NSC. Data were analyzed using SAS's General Linear Model (GLM) procedures (version 9.4, 2019). The result indicates that the increasing level of MFL had no significant effect on basal dry matter intake. The apparent digestibility of DM was higher (P<0.001) in T1 (60.5%) and T6 (62.5%); a higher (P<0.001) average daily gain was recorded for animals in T6 (171.0g/d). The cost-benefit analysis revealed that T5 has a good and optimum final body weight gain (30.5kg), 765.5 ET/head total return, and 381.1 ETB/head net return. It was concluded that 25% inclusion of MFL in the diet increases nutrient intake, weight gain and economic efficiency in Bonga sheep.

Understanding the factors which control endothelial cell (EC) function and angiogenesis in the horse is crucial for developing the horse as a disease model but equine ECs remain poorly studied. In this study we have optimised methods for the isolation and culture of equine aortic endothelial cells (EAoECs) and characterised their angiogenic functions in vitro. Mechanical dissociation, followed by magnetic purification using an anti-VE-cadherin antibody, resulted in EC-enriched cultures suitable for further study. Fibroblast growth factor 2 (FGF2) increased EAoEC proliferation rate and stimulated scratch wound closure and tube formation by EAoECs on extracellular matrix. Pharmacological inhibitors of FGFR1 (SU5402) or MEK (PD184352) blocked FGF2-induced ERK1/2 phosphorylation and functional responses, suggesting that these are dependent on FGFR1/MEK-ERK signalling. In marked contrast, VEGF-A had no effect on EAoEC proliferation, migration or tubulogenesis and did not promote ERK1/2 phosphorylation, indicating a lack of sensitivity to this classical pro-angiogenic growth factor. Gene expression analysis showed that, unlike human ECs, FGFR1 is expressed by EAoECs at a much higher level than both VEGFR1 and VEGFR2. These results suggest a predominant role for FGF2 versus VEGF-A in controlling the angiogenic functions of equine ECs. Collectively, our novel data provide a sound basis for studying angiogenic processes in the horse and lay the foundations for comparative studies of EC biology in horses versus humans.

Background: HIV is accompanied by production of proinflammatory cytokines which are regarded as critical in neuronal damage, leading to brain dysfunction, hence the need to identify cytokine biomarkers sensitive to brain damage. Methods: We applied MRI volumetric neuroimaging and high throughput Luminex based immunoassays to examine the relationship between cortical white matter, subcortical gray matter and total gray matter brain volumes and plasma cytokines in HIV indviduals using generalised linear models and Partial least square regression model. Results: Higher plasma inflammatory cytokines CCL5/RANTES and MCP-1 were significantly associated with lower cortical white matter volume. Higher IL-6 was associated with both lower subcortical gray matter and lower total gray matter, whereas higher IL-8 and GM-CSF were associated with lower total gray matter only. Higher VEGF, PDGF-BB and IL-9 were associated with higher cortical white matter volumes. After standardisation and adjusting for clinical and demographic variables, IL-6, IL-8, MCP-1 remained associated with lower volumes of the three brain regions whereas IL-9, VEGF and PDGF-BB were associated with higher volumes. Conclusions: Association proinflammatory cytokines RANTES, MCP-1 and IL-6 with lower brain volumes could imply possible involvement in neurodegerative processes in HIV infection while IL-9, VEGF and PDGF may have a neuroprotective or neurotrophic role.

Phenylketonuria (PKU) is an inherited disorder of protein metabolism. It is generally treated using dietary management with limited intake of phenylalanine (Phe). Partial breastfeeding (BF) is encouraged among mothers of infants with PKU, together with a Phe-free mixture of synthetic amino acids. We aimed to describe our current BF rates and complementary feeding practices, as well as examining parental experiences of infant feeding. The aim was to better understand the challenges faced by families so improvements can be made to clinical care. A chart review was carried out on 39 PKU patients, examining the BF rate and duration, use of second stage synthetic protein (SP) and average complementary feeding age. A parental questionnaire on complementary feeding and BF experience was designed. 26% of babies were partially breastfed at three months. 70% of mums would like to have breastfed for longer and cited PKU as a reason for stop-ping. 52% parents reported challenges during the complementary feeding process including food refusal, protein calculation and anxiety around maintaining good Phe levels. Suggestions to improve BF continuation and duration include active promotion of the benefits and suitability, access to lactation consultant and peer support. The delay in introducing a second stage SP may contribute to long-term bottle use for SP. Improved patient education, written resources and sup-port is necessary to improve food choices and long term acceptance of SP.

Social media HPV vaccination interventions show promise for increasing HPV vaccination rates. An important consideration for the implementation of effective interventions into real-world practice in the translation potential, or external validity, of the intervention. To this end, we conducted a systematic literature review to describe the current body of evidence regarding the external validity of social media HPV vaccination-related interventions. Constructs related to external validity were based on the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework. Seventeen articles published between 2006 and 2020 met inclusion criteria. Three researchers independently coded each article using a validated RE-AIM (reach, effectiveness/efficacy, adoption, implementation, maintenance) framework. Discrepant codes were discussed with a fourth reviewer to gain consensus. Of these 17 studies, three were pilot efficacy studies, 10 were RCTs to evaluate effectiveness, one was a population-based study, and three did not explicitly state which type of study was conducted. Reflecting this distribution of study types, across all studies the mean level of reporting RE-AIM dimensions varied with reach recording 90.8%, effectiveness (72.1%), adoption (40.3%), implementation (45.6%), and maintenance (26.5%). This review suggests that while the current HPV vaccination social media-driven interventions provide sufficient information on internal validity (reach and effectiveness), few have aimed to gather data on external validity needed to translate the interventions into real world implementation. Our data suggest that implementation research is needed to move HPV vaccination-related interventions into practice. Included in this review are recommendations for enhancing the design and reporting of these HPV vaccination social media-related interventions.

Tightly regulated and robust mitochondrial activities are critical for normal hearing. Previously, we demonstrated that Fus1 KO mice with mitochondrial dysfunction exhibit premature hearing loss. Molecular analysis of the cochlea revealed hyperactivation of the mTOR pathway, oxidative stress, altered mitochondrial morphology and quantity, suggesting compromised energy sensing and production. Here, we investigated whether pharmacological modulation of metabolic pathways using rapamycin (RAPA) or 2-deoxy-D-glucose (2-DG) supplementation can protect against hearing loss in female Fus1 KO mice. Additionally, we aimed to identify mitochondria- and Fus1-dependent molecular pathways and processes critical for hearing. We found that inhibiting mTOR or activating alternative mitochondrial energetic pathways to glycolysis protected hearing in the mice. Comparative gene expression analysis revealed dysregulation of critical biological processes in the KO cochlea, including mitochondrial metabolism, neural and immune responses, and cochlear hypothalamic–pituitary–adrenal axis signaling system. RAPA and 2-DG mostly normalized these processes, although some genes showed a drug-specific response or no response at all. Interestingly, both drugs resulted in a pronounced upregulation of critical hearing-related genes not altered in the non-treated KO cochlea, including cytoskeletal and motor proteins, and Ca2+-linked transporters and voltage-gated channels. These findings suggest that pharmacological modulation of mitochondrial metabolism and bioenergetics may restore and activate processes critical for hearing, thereby protecting against hearing loss

The sustainability of agriculture depends as much on the natural resources required for production as it does on the stakeholders that manage those resources. It is thus essential to understand the variables that influence the decision-making process of agricultural stakeholders to design educational programs, interventions, and policies geared towards their specific needs, a required step to enhance agricultural sustainability. We examined the perceptions, experiences, and priorities that influence management decisions of five major groups of agricultural stakeholders (conventional small grain producers, organic small grain producers, organic vegetable producers, extension agents and agro-industry crop consultants, and researchers) across the Montana, United States. Results revealed that while stakeholder groups have distinct perceptions, experiences, and priorities, there were similarities across groups. Specifically, organic vegetable and organic small grain producers showed similar responses that were, in turn, divergent of conventional producers, researchers, and crop consultants. Conventional small grain producers and researchers showed overlapping response patterns while crop consultants formed an isolated group. Our results reinforce the need for agricultural education and programs that address unique and shared experiences, priorities, and concerns of multiple stakeholder groups. This study endorses the call for a paradigm shift from the traditional top-down agricultural extension model to one that accounts for participants’ socio-ecological contexts to facilitate the adoption of sustainable agricultural systems that support environmental and human wellbeing.

Electricity distribution network operators face several operational constraints in the provision of safe and reliable power given that investments for network area reinforcement must be commensurate with improvements in network reliability. This paper provides an integrated approach for assessing the impact of different operational constraints on distribution network reliability by incorporating component lifetime models, time-varying component failure rates as well as the monetary cost of customer interruptions in an all-inclusive probabilistic methodology that applies a time-sequential Monte Carlo simulation. A test distribution network based on the Roy Billinton test system is modelled to investigate the system performance when overloading limits are exceeded as well as when preventive maintenance is performed. Standard reliability indices measuring the frequency and duration of interruptions, and the energy not supplied are complemented with a novel monetary reliability index. The comprehensive assessment includes not only average indices but also their probability distributions to adequately describe the risk of customer interruptions. Results demonstrate the effectiveness of this holistic approach as the impacts of operational decisions are assessed from both reliability and monetary perspectives. This informs network planning decisions through optimum investments and consideration of customer outage costs.

Over the past decades, research has escalated on the use of polylactic acid (PLA) as replacement for petroleum-based polymers. This is due to its valuable properties, such as renewability, biodegradability, biocompatibility and good thermomechanical properties. Despite possessing good mechanical properties comparable to conventional petroleum-based polymers, PLA suffers from some shortcomings such as low thermal resistance, heat distortion temperature and rate of crystallization, thus different fillers have been used to overcome these limitations. In the frame work of environmentally friendly processes and products, there has been growing interest on the use of cellulose nanomaterials viz. cellulose nanocrystals (CNC) and nanofibers (CNF) as natural fillers for PLA towards advanced applications other than short-term packaging and biomedical. Cellulosic nanomaterials are renewable in nature, biodegradable, eco-friendless and they possess high strength and stiffness. In the case of eco-friendly processes, various conventional processing techniques, such as melt extrusion, melt-spinning, and compression moulding, have been used to produce PLA composites. This review addresses the critical factors in the manufacturing of PLA-cellulosic nanomaterials by using conventional techniques and recent advances needed to promote and improve the dispersion of the cellulosic nanomaterials. Different aspects, including morphology, mechanical behavior and thermal properties, as well as comparisons of CNC- and CNF reinforced PLA, are also discussed

The main aim of the present study was to explore health professionals’ reported experiences and approaches to managing children who receive a designation of cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/cystic fibrosis screen positive inconclusive diagnosis following a positive NBS result for cystic fibrosis. An online questionnaire was distributed via Qualtrics Survey Software and circulated to a purposive, international sample of health professionals involved in managing children with this designation. In total, 101 clinicians completed the online survey; 39 from the US, six from Canada and 56 from Europe (including the UK). Results indicated that while respondents reported minor deviations in practice, they were cognizant of recommendations in the updated guidance and for the most part, attempted to implement these into practice consistently internationally. Where variation was reported, the purpose of this appeared to be to enable clinicians to respond to either clinical assessments or parental anxiety in order to improve outcomes for the child and family. Further research is needed to determine if these findings are reflective of both a wider audience of clinicians and actual (rather than reported) practice.

Targets for finished livestock are often determined by expected fat, either subcutaneous or intramuscular. These targets are used frequently to improve the chances of acceptable eating quality. Lower intramuscular fat, lack of product uniformity, and reduced or insufficient tenderness can negatively impact beef acceptability. This study aimed to investigate differences in gene expression that potentially alter subsequent metabolism and intercellular signaling in the muscle and proximate intermuscular and subcutaneous adipose tissue in beef carcasses at different fat endpoints. In this study, Longissimus thoracis muscle samples and associated adipose tissue were collected at harvest. RNA was harvested from both tissues, and individual samples were sequenced using RNAseq. Differential expression was determined using edgeR, and p-values were adjusted using the Benjamini-Hochberg method. A corrected p-value of 0.005 and log₂ (fold change) of 1 was set as the threshold to identify differential expression of genes. Comparison between intermuscular fat and subcutaneous fat showed no differences between the genes activated in the two adipose tissue depots, suggesting that subcutaneous fat could be sampled to evaluate changes in adipose tissue. Carcass data allowed the classification of carcasses by projected USDA quality grades (marbling targets). In the comparison between muscle from Standard and Choice carcasses, 15 genes were downregulated, and 20 were upregulated. The insulin receptor substrate 1 (IRS 1) gene was the only known functionally important gene to be differentially expressed. There were 49 downregulated genes and 113 upregulated genes in the comparison between adipose tissue from Standard and Choice carcasses. These genes are mostly related to the metabolism of fat and energy. This potentially indicates that muscle is not changing at the transcript level as much as the adipose tissue at the sampled endpoints. Also, subcutaneous fat can be used to evaluate transcript changes in both subcutaneous and intermuscular fat. However, it is not clear if these fat tissues can be used as surrogates for intramuscular fat or marbling.

Periodontal disease is one of the most common conditions affecting dogs worldwide and is reported to be particularly prevalent in racing greyhounds. A range of potential risk factors have been hypothesised. Previous research has suggested, regular tooth brushing can reduce both calculus and gingivitis, but the frequency required is unclear. Here, we report a controlled blinded in-situ in which kennel staff brushed 160 racing greyhounds’ teeth (living at six kennel establishments), either weekly, daily or never over two-month period. All visible teeth were scored for calculus and gingivitis, using previously validated scales. We calculated average scores for each of three teeth groups and overall averaging the teeth groups. Changes were compared to baseline. After two months, the total calculus scores (controlling for baseline) were significantly different in the three treatemnet groups, (F(2,129) = 10.76, p&lt;0.001) with both weekly and daily brushing resulting in significant reductions. Gingivitis was also significantly different (F(2,128) = 4.57, p=0.012), but in this case, only daily brushing resulted in a significant reduction. Although dogs in different kennels varied significantly in their levels of both calculus (F(5,129) =8.64, p&lt;0.001), and gingivitis (F(5,128)=3.51 p=0.005), the intervention was generally similarly effective in all establishments. Teeth groups varied and incisors were not significantly affected by treatment. Since trainers implementing the routine, reported minimal time commitment and positive experiences, we suggest that daily brushing is recommended for racing greyhounds, and that demonstrations should include attention to all teeth groups including incisors. Similar trials need to be conducted with retired greyhounds since these have been shown to present particularly high levels of periodontal disease.

Microbiota-based strategies are a novel auxiliary therapeutic and preventative way of moderating chronic kidney disease. Lactobacillus mixture (Lm) was previously demonstrated to exert a renal-protective function in the CKD mice model. The efficacy of probiotics in pet foods is a relatively new area of study, and thus verifying the potential health benefits is necessary. This study evaluated the efficacy of Lm treats in feline CKD and elucidated the mechanisms underlying host-microbe interactions. CKD cats (2 and 3 stages) were administrated probiotic pet treats daily (10 g) for 8 weeks. The results demonstrated that during the eight weeks of Lm administration, creatinine was reduced or maintained in all cats with CKD. Similarly, gut-derived uremic toxins (GDUT), IS, and TMAO were significantly downregulated in the serum (confidence intervals = 90%). The life quality of the cats also improved. Feline gut microbiome data, KEGG pathway, and renal function indicator analyses revealed the possible mechanisms involved in modulating CKD feline microbial composition. Further regulation of the microbial functions in amino acid metabolism after Lm administration contributed to downregulating deleterious IS, PCS, and TMAO. The current study provides potential adjuvant therapeutic insights into probiotic pet foods or treats for pets with CKD.

The bioactive marine sulfated polysaccharides ulvan and carrageenan, formulated in gels at 1.5, 5.0 and 10% w/w concentrations, were evaluated for their wound healing potential on second-degree burn wounds. The polysaccharide-based gels were administered on the burn-inflamed skin of hairless female SKH-hr2 mice, and the therapeutic effect of the various treatments was assessed based on histopathological analysis, the clinical condition of mice, photo-documentation, evaluation of biophysical skin parameters, and FT-IR spectroscopy.Clinical and histopathological assessment, as well as the reduction rate of the burn wound area, indicated that the 10% w/w carrageenan gel significantly enhanced wound healing, especially at the early stages of the healing process, recovering both the α-helix of collagen and the glycosaminoglycans configuration as evidenced by the FT-IR absorption bandsof skin in vivo and ex vivo. At later stages, the healing effect of the 5% w/w ulvan gel was also notably significant, indicating that carrageenan and ulvan wound dressing gels could potentially contribute to the efficient wound healing of burn wounds.

Different studies corroborate a role for ceramide synthases and their downstream products, ceramides, in modulation of apoptosis and autophagy in the context of cancer. These mechanisms of regulation, however, appear to be context dependent in terms of ceramides’ fatty acid chain length, subcellular localization, and the presence or absence of their downstream targets. Our current understanding of the role of ceramide synthases and ceramides in regulation of apoptosis and autophagy could be harnessed to pioneer the development of new treatments to activate or inhibit a single type of ceramide synthase, thereby regulating the apoptosis induction or cross talk of apoptosis and autophagy in cancer cells. Moreover, the apoptotic function of ceramide suggests that ceramide analogues can pave the way for the development of novel cancer treatments. Therefore, in the current review paper we discuss the impact of ceramide synthases and ceramides in regulation of apoptosis and autophagy in context of different types of cancers. We also briefly introduce the latest methods to analyze the lipids in biological samples. Finally, we discuss the drug development strategies focusing on the ceramide synthases and ceramides as future therapeutic approaches in cancer therapy.

2-(4-Benzyloxy-3-methoxyphenyl)-5-(carbethoxyethylene)-7-methoxy-benzofuran (BMBF), a benzofuran derivative, is an intermediate found in the process of total synthesis of ailanthoidol. Benzofuran derivatives are a class of compounds that possess various biological and pharmacological activities. The present study explored the anti-metastasis effects in hepatocellular carcinoma (HCC). Our preliminary findings indicate that BMBF suppresses the proliferation and changes the morphology of Huh7, an HCC cell line with a mutated p53 gene (Y220C). According to scratching motility assay, noncytotoxic concentrations of BMBF significantly inhibited the motility and migration in Huh7 cells. BMBF upregulated the expression of E-cadherin and downregulated the expression of vimentin, Slug, and MMP9, which are associated with epithelial-mesenchymal-transition (EMT) and metastasis in Huh7 cells. BMBF decreased the expression of integrin α7 and deactivated its downstream signal FAK/AKT and inhibited p53 protein levels. Cell transfection with p53 siRNA resulted in prevention of cell invasion because of the reduced expression of integrin α7, Slug, and MMP-9 in Huh7 cells. BMBF had anti-metastatic effects in PLC/PRF/5, an HCC cell line with R249S, a mutated p53 gene. Our findings indicate that BMBF has anti-metastatic effects in that it downregulates p53 and mediates the suppression of integrin α7, EMT, and MMP-9 in HCC cells with mutated p53 gene.

Transportation authorities aim to boost road safety by identifying risky locations and applying suitable safety measures. The Highway Safety Manual (HSM) is a vital resource for US transportation professionals, aiding in the creation of Safety Performance Functions (SPFs), which are predictive models for crashes. These models rely on Negative Binomial distribution-based regression and misinterpreting them due to unmet statistical assumptions can lead to erroneous conclusions, including inaccurately assessing crash rates or missing high-risk sites. The Florida Department of Transportation (FDOT) has introduced context classifications to HSM SPFs, complicating assumption violation identification. This study, part of an FDOT-sponsored project, investigates established statistical diagnostic tests to identify model violations and proposes a novel approach to determine optimal spatial regions for Empirical Bayes adjustment. This adjustment aligns HSM-SPFs with regression assumptions. The study employs a case study involving Florida roads. Results indicate that a 20-mile radius offers an optimal spatial sample size for modeling crashes of all injury levels, ensuring accurate assumptions. For severe injury crashes, which are less frequent and harder to predict, a 60-mile radius is suggested to fulfill statistical modeling assumptions. This methodology guides FDOT practitioners in assessing the conformity of HSM-SPFs with intended assumptions and determining appropriate region sizes.

TGF-ꞵ signaling is a vital regulator for maintaining articular cartilage homeostasis. Runx transcription factors, downstream targets of TGF-ꞵ signaling, have been studied in the context of osteoarthritis (OA). Although Runx partner core binding factor β (Cbfβ) is known to play a pivotal role in chondrocyte and osteoblast differentiation, the role of Cbfβ in maintaining articular cartilage remains obscure. This study investigated Cbfβ as a novel anabolic modulator of TGF-ꞵsignaling and determined its role in articular cartilage homeostasis. Cbfβ significantly decreased in aged mouse articular cartilage and human OA cartilage. Articular chondrocyte-specific Cbfb-deficient mice (Cbfb△ac/△ac) exhibited early cartilage degeneration at 20 weeks old and developed OA at 12 months old. Cbfb△ac/△ac mice showed enhanced OA progression under the surgical-induced mice OA model. Mechanistically, forced expression of Cbfβ rescued Col2α1 and Runx1 expression in Cbfβ-deficient chondrocytes. TGF-ꞵ1-mediated Col2α1 expression failed despite the pSmad3 activation under TGF-ꞵ1 treatment in Cbfβ-deficient chondrocytes. Cbfβ protected Runx1 from proteasomal degradation through Cbfβ/Runx1 complex formation. These results indicate that Cbfβ is a novel anabolic regulator for cartilage homeostasis, suggesting that Cbfβ could protect OA development by maintaining the integrity of the TGF-ꞵ1 signaling pathway in articular cartilage.

Scrub typhus is a life-threatening infectious disease and always creating a diagnostic dilemma in terms of rapid turnaround time and accuracy, qRT PCR can become a very good option to achieve the desired result with the molecular level of accuracy and boost up the rapid patient management. This study was performed to evaluate the performance of qRT PCR in comparison to commonly used IgM ELISA and Weil-Felix tests to diagnose scrub typhus, as well as to look for the demographic and clinical profile of the disease in North-East India. It was a hospital-based prospective study conducted in a tertiary care hospital of north-east India, over a period of 1 year, in which all the samples from suspected scrub typhus cases were screened by Weil-Felix test as per institute’s diagnostic protocol after which IgM ELISA for Scrub Typhus was performed. All the IgM positive samples and 20 highly suspected but ELISA negative samples were subjected to qRT PCR, targeting 56 kDa type-specific gene of O. tsutsugamushi. Statistical analysis was done by MS-Excel for Windows v2013® and MedCalc® v17.9 for Windows (MedCalc Software, Acacialaan 22, B-8400 Ostend, Belgium). In this study, we have successfully evaluated the performance of qRT PCR kit for diagnosis of scrub typhus. Out of 54 samples tested, 24 IgM ELISA positive samples and 3 IgM ELISA negative samples have shown the presence of bacterial DNA with quantification of DNA copies. It has also been observed that 21 out of 27 PCR positive samples (77.8%) were detected within the 1st 7 days of illness. All the demographic, as well as clinical data, were also analysed. The performance of the commercial qRT PCR kit used in our study is satisfactory, which provides the extra advantage of quantification of DNA copies and increases diagnostic accuracy within the 1st week of fever.

This contribution shows the possibilities of a low-cost multipurpose data logger that was built around an Arduino Mega 2560 single board computer. To transform the Arduino Mega into such a data logger, a sensor shield was designed that contains an SD-card, real-time clock, and different kinds of connectors so that sensors can easily be attached to the device. The software considers a wide range of predefined sensors from which a user can choose. To assess the performance of such a device, short-term monitoring campaigns in relation to outdoor air quality, human activity in an office, motion of a journey on a bike, and exhaust gas monitoring of a diesel generator were realized. Besides the possibilities to apply the data logger in different kinds of applications, a method is proposed to assess the credibility of such a system. The assessment based on the various short-term campaigns showed that the system scores positively on most of the performance indicators, but that unexpected (black swan) events affect the assessment over the longer term. This makes the development of low-cost scientific instruments harder than expected. The stability and long-term performance of this type of design requires continuous evaluation and engineering correction.

Fanconi anemia (FA) develops due to a mutation in one of the FANC genes that are involved in repair of interstrand crosslinks (ICLs). FANCG, a member of the FA core complex, is essential for ICL repair. Previous FANCG-deficient mouse models were generated with drug-based selection cassettes in mixed mice backgrounds, leading to a disparity in interpretation of genotype-related phenotype. To exclude these confounders, we created a Fancg-KO (KO) mouse model using CRISPR/Cas9. The entire Fancg locus was targeted and maintained on the immunological well-characterized C57BL/6J background. Intercrossing of heterozygous mice resulted in sub-Mendelian numbers of homozygous mice, suggesting loss of FANCG can be embryonic lethal. KO mice displayed infertility, hypogonadism but no other developmental problems. Bone marrow analysis revealed a defect in various hematopoietic stem and progenitor subsets with a bias towards myelopoiesis. Cell lines derived from Fancg-KO mice were hypersensitive to crosslinking agents-cisplatin and Mitomycin C, and Fancg-KO mouse embryonic fibroblasts (MEFs) displayed increased γ-H2AX upon cisplatin treatment. Reconstitution of these MEFs with Fancg cDNA corrected for the ICL hypersensitivity. Collectively, this project provides a new, genetically and immunologically well-defined Fancg-KO mouse model for further in vivo and in vitro studies on FANCG and ICL repair.

The goal was to determine the personal, interpersonal, and sociocultural predictors of condom use among rural indigenous adolescents. Predictor variables were selected from Bandura's Social Cognitive Theory and Leininger's Transcultural Theory. The sample consisted of 419 Nahuas adolescents randomly selected from the total number of neighborhood blocks in a rural community in Puebla, Mexico. The instruments had acceptable psychometric characteristics (Cronbach alpha and validity scores). Multiple linear regression models were used. Results: 56.8% of participants were female, and 50.40 % were students. The mean age was M = 17.5 (SD = 0.97), and the majority (63%) identified as Catholic. Age at menarche/first ejaculation (β = -1.2, p = .038), attitude toward condom use (β = .13, p < .001), ethnic identity (β = .21, p < .001), and ability to negotiate condom use (β = .13, p < .003), predicted (R2 = 22.3) condom use. This study provides a basis for the integration of the cultural values of indigenous adolescents within interventions for sexual health promotion.

Background: The most frequent non-pigmented malignancy of the ocular surface is ocular surface squamous neoplasia (OSSN), which has a frequency of 0.03 to 1.9 per 100,000 people per year. It can be diagnosed histologically as anything from mild dysplasia to aggressive squamous cell carcinoma that affects both the conjunctiva and the cornea. The purpose of this study is to determine the distribution of ocular surface squamous neoplasia at a teaching hospital in South Western Uganda.Methods: In this retrospective study, we reviewed all records of patients with ocular surface squamous neoplasia from the Mbarara University of Science and Technology (MUST)/ Mbarara Regional Referral Hospital (MRRH) pathology laboratory in South Western Uganda, from January 2015- October 2021.Results: Of the 1,133 cases of ocular neoplasia seen during this time, OSSN composed of 26.7% (n=303). OSSN occurred mainly in females (59.1%). The most common OSSN was invasive squamous cell carcinoma (60.4%). The age range was 15-106 years while the mean was 39.99 years. The commonest affected age group was 30-44years (41.3%).Conclusion: The burden of OSSN is high. It primarily affects young adults and is frequently found in women. Squamous cell carcinoma makes up the majority of the disease.

Technologies providing copyright-infringing IPTV content are a commonly used, as an illegal alternative to legal IPTV subscriptions and services, as they usually have lower monetary costs, and can be more convenient for the users that follow content from different sources. These infringing IPTV technologies may include websites, software, software add-ons, and physical set-top boxes. Due to the free or low cost of illegal IPTV technologies, illicit IPTV content providers will often resort to intrusive advertising, scams, and the distribution of malware to increase their revenue. We developed an automated solution for collecting and analysing malware from illegal IPTV technologies and used it to analyse a sample of illicit IPTV websites, application (app) stores, and software. Our results show that our IPTV Technologies Malware Analysis Framework (IITMAF) classified 32 of the 60 sample URLs tested as malicious, compared to running the same test using publicly available online anti-virus solutions, which only detected 23 of the 60 sample URLs as malicious. Moreover, the IITMAF framework also detected malicious URLs and files from 31 of the sample’s websites, one of which had reported ransomware behaviour.

The utilization of person centered care is highlighted as essential for health promotion, yet implementation has been inconsistent and multiple issues remain. There is a dearth of applied re-search exploring the facets of successful implementation. In this paper, a person centered wellbeing program spanning various groups is discussed outlining the central principles that have allowed for successful outcomes. The main data emerges from 10 years of pragmatic pre-post service evaluation. Measures of functional capacity and wellbeing were captured using validated measures. The method for this paper is a narrative exploration of the theory and practices that can explain the continual improvement the clinics have achieved over 10 years. Core principles relate to connecting with people, connecting through groups, and connecting with self. The operationalization and theoretical explanation of these principles is outlined alongside 10 years of data which shows sustained improvement in a range of outcomes. The discussion of these principles posits essential factors to prioritize to advance the implementation of person centered care in health promotion for long term conditions.

Modern drugs have changed epilepsy, which affects people of all ages. But for young people with epilepsy, the framework of drug development has stalled. In the wake of the thalidomide catastrophe, the misconception emerged that for people <18y antiseizure medications (ASMs) need separate proof of efficacy and safety (E&S), overall called “pediatric drug development.” This has been corrected to some extent. Authorities accept that ASMs are effective in <18y as well, but they still require "extrapolation of efficacy," as if minors were another species. In our view, the real problem is less that relevant parts of pediatric clinical epilepsy research over the past decades were useless, but that this has hampered research on meaningful challenges. We do not need to show that ASMs work also before the 18th birthday. But we need to learn how to best use ASMs to prevent brain damage in young patients and optimize ASMs use considering a broader range of aspects

Full-order state-space models represent the starting point for the development of advanced control methods for wind turbine systems (WTSs). Regarding existing control-oriented WTS models, two research gaps must be noted: (i) There exists no full-order WTS model in form of one overall ordinary differential equation that considers all dynamical effects which significantly influence the electrical power output; (ii) all existing reduced-order WTS models are subject to rather arbitrary simplifications and are not validated against a full-order model. Therefore, in this paper, two full-order nonlinear state-space models (of 11th and 9th-order in the (a, b, c)- and (d, q)-reference frame, resp.) for variable-speed variable-pitch permanent magnet synchronous generator WTSs are derived. The full-order models cover all relevant dynamical effects with significant impact on the system’s power output, including the switching behavior of the power electronic devices. Based on the full-order models, by a step-by-step model reduction procedure, two reduced-order WTS models are deduced: A non-switching (averaging) 7th-order WTS model and a non-switching 3rd-order WTS model. Comparative simulation results reveal that all models capture the dominant system dynamics properly. The full-order models allow for a detailed analysis covering the high frequency oscillations in the instantaneous power output due to the switching in the power converters. The reduced-order models provide a time-averaged instantaneous power output (which still correctly reflects the energy produced by the WTS) and come with a drastically reduced complexity making those models appropriate for large-scale power grid controller design.

Mitochondrial dysregulation is implicated in numerous neurological disorders. Mitochondrial dynamics, including biogenesis, fusion and fission, are essential components of mitostasis which is modulated by complex regulatory mechanisms. Although expression studies are often used to investigate mitochondrial dynamics, these studies may be limited by the interdependent and temporal nature of mitostasis. Transmission electron microscopy (TEM) and cryogenic preparation methods provide a direct approach to examine mitochondrial ultrastructure in neurons. We investigated the utility of TEM to visualize mitochondrial morphological changes in SH-SY5Y cells treated with propionic acid (PPA). We examined whether morphological alterations were associated with differences in membrane potential or expression of biogenesis, fusion and fission genes. PPA induced a significant decrease in mitochondrial area (p<0.01 5mM), Feret's diameter and perimeter (p<0.05 5mM), and in area2 (p<0.05 3mM, p<0.01 5mM) – consistent with a shift towards fission. Morphological changes were not associated with significant differences in mitochondrial membrane potential. However, we observed decreased gene expression of NRF1 (p<0.01), TFAM (p<0.05), and STOML2 (p<0.0001). These data support a disruption of the balance in dynamics to preserve function under stress. This demonstrates the utility of TEM to provide insight into mitochondrial dynamics and function which can inform targeted mechanistic investigations into neuropathology.

How robust is our assessment of impacts to ecosystems and species from a rapidly changing climate during the 21st century? We examine the challenges of uncertainty, complexity and constraints associated with applying climate projections to understanding future biological responses. This includes an evaluation of how to incorporate the uncertainty associated with different greenhouse gas emissions scenarios and climate models, and constraints of spatiotemporal scales and resolution of climate data into impact assessments. We describe the challenges of identifying relevant climate metrics for ecological models and evaluate the usefulness and limitations of different methodologies of applying climate change to both quantitative and qualitative ecological response models. We discuss the importance of incorporating extreme climate events and their stochastic tendencies in assessing ecological impacts and transformation, and provide recommendations for better integration of complex climate-ecological interactions at relevant spatiotemporal scales. We further recognize the compounding nature of uncertainty when accounting for our limited understanding of the interactions between climate and biological processes. Given the inherent complexity in ecological processes and their interactions with climate, we recommend integrating quantitative modeling with expert elicitation from diverse disciplines and experiential understanding of recent climate-driven ecological processes to develop more robust understanding of ecological responses under different scenarios of future climate change. Inherently complex interactions between climate and biological systems also provide an opportunity to develop wide-ranging strategies that resource managers can employ to prepare for the future.

The process of revitalising quiescent cells in order for them to proliferate plays a pivotal role in the repair of warn out tissues as well as for tissue homeostasis. This process is also crucial in the growth, development and well-being of higher multi-cellular organisms such as mammals. Deregulation of quiescent-proliferation transition is related to many diseases, in particular cancer. Recent studies have revealed that this process is regulated tightly by the Rb−E2F bistable switch mechanism. Based on experimental observations, in this study, we formulate a mathematical model to examine the effect of the growth factor concentration on the proliferation-quiescence transition in human cells. Working with a non-dimensionalised model, we prove positivity, boundedness and uniqueness of solutions. To understand model solution behaviour close to bifurcation points, we carry out bifurcation analysis, which is further verified by use of numerical bifurcation analysis, sensitivity analysis and numerical simulations. Indeed, bifurcation and numerical analysis of the model predicted a transition between stable, bistable and stable states, which are dependent on the growth factor concentration parameter (GF). The derived predictions confirm experimental observations.

Viral integration within the host genome plays a pivotal role in carcinogenesis. Various disruptive mechanisms are involved, leading to genomic instability, mutations, and DNA damage. With next-generation sequencing (NGS), we can now precisely identify viral and host genomic breakpoints and chimeric sequences, which are useful for integration site analysis. In this study, we evaluated a commercial hybrid-capture NGS panel specifically designed for detecting three key viruses: HPV, HBV, and HIV-1. We also tested workflows for Viral Hybrid Capture (VHC) and Viral Integration Site (VIS) analysis, leveraging customized viral databases in CLC Microbial Ge-nomics. By analyzing sequenced data from virally infected cancer cell lines (including SiHa, HeLa, CaSki, C-33A, DoTc2, 2A3, SCC154 for HPV; 3B2, SNU-182 for HBV; and ACH-2 for HIV-1), we precisely pinpointed viral integration sites. The workflow also highlighted disrupted and neigh-boring human genes that may play a crucial role in tumor development. Our results included in-formative virus-host read mappings, genomic breakpoints, and integration circular plots. These visual representations enhance our understanding of the integration process. In conclusion, our seamless end-to-end workflow bridges the gap in understanding viral contributions to cancer development, paving the way for improved diagnostics and treatment strategies.

Visceral leishmaniasis (VL) is a severe parasitic disease transmitted by phlebotomine sandflies. VL is endemic in West Pokot County, Kenya, where effective strategies to interrupt transmission are impeded by the limited understanding of VL risk factors. Therefore, this case-control study aimed to explore environmental, behavioral and household determinants of VL in West Pokot. From November 2022 to January 2023, a structured questionnaire was administered to 36 symptomatic primary VL cases attending the Kacheliba Sub-County Hospital and to 50 controls from local villages. The VL status of all participants was confirmed using an rK39 rapid diagnostic test. In an age-corrected univariate logistic regression analysis, significant associations were found between VL and housing characteristics, such as window presence and floor type. Furthermore, outdoor activities, including traveling outside the residence for more than 2 weeks, activities near termite mounds, and forest activities during the rainy season increased the risk of VL. VL cases more frequently reported the presence of cattle, dogs and sheep in their house yards at night. VL was also associated with cutting down trees in the house yard and house proximity to several Acacia tree species. To conclude, this work reports a number of previously undescribed risk factors for VL in the understudied West Pokot focus. Our findings warrant further research into sandfly ecology and potential zoonotic parasite reservoirs in West Pokot.

Background. Candida bloodstream infections (CBSIs) have decreased among pediatric populations in the United States, but remain an important cause of morbidity and mortality. Species distributions and susceptibility patterns of CBSI isolates diverge widely between children and adults. Awareness of these patterns can inform clinical decision-making for empiric or pre-emptive therapy of children at risk for candidemia. Methods. CBSIs occurring from 2006-2016 among patients in a large children’s hospital were analyzed for age specific trends in incidence rate, risk factors for breakthrough-CBSI and death, as well as underlying conditions. Candida species distributions and susceptibility patterns were evaluated in addition to antifungal agent use. Results. The overall incidence rate of CBSI among this complex patient population was 1.97/1,000 patient-days. About half of CBSI episodes occurred in immunocompetent children and 14% in Neonatal Intensive Care Unit (NICU) patients. Antifungal resistance was minimal: 96.7% of isolates were fluconazole-, 99% were micafungin-, and all were amphotericin susceptible. Liposomal amphotericin was the most commonly prescribed antifungal agent including for NICU patients. Overall CBSI-associated mortality was 13.7%; there were no deaths associated with CBSI among NICU patients after 2011. Conclusions. Pediatric CBSI characteristics differ substantially from those in adults. Improved management of underlying diseases and antimicrobial stewardship may further decrease morbidity and mortality from CBSI while continuing to maintain low resistance rates among Candida isolates.

This paper reports on in-depth qualitative interviews conducted with 69 disabled people in England and Scotland, and with 28 key informants from infrastructure organisations in the voluntary and statutory sectors, about the impact of COVID-19, and measures taken to control it. Participants were recruited through voluntary organisations. As with everyone, the Pandemic has had a huge impact: we discuss the dislocations it has caused in everyday life; the failures of social care; the use of new technologies; and participants’ view on leadership and communication. We conclude with suggestions for urgent short term and medium term responses, so that the United Kingdom and other countries can respond better to this and other pandemics, and build a more inclusive world.

Since the outbreak of the COVID-19 (Coronavirus Disease 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2). The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit the Main Protease (M^pro) and Spike (S) glycoprotein of SARS-CoV-2. The evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. A rule of five (RO5) was calculated to determine whether a compound meets the criteria as an active drug orally in humans. The determination of the docking score was done by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs' free energy of binding / ΔG). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. The results showed that hesperidin, nabiximols, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine, and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and nabiximols had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as M^pro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine, and hydroxychloroquine sulfate which so far are recommended in the treatment of COVID-19. As judged by the RO5 and previous study by others, the compounds kaempferol, herbacetin, eugenol, and 6-shogaol have good oral bioavailability, so they are also seen as promising candidates for the development lead compounds to treat infections caused by SARS-CoV-2.

Background: Although previous studies have implicated a role for the stool microbiome in cancer cachexia, the fecal microbiome has not been previously characterized for patients with pancreatic ductal adenocarcinoma (PDAC) and cachexia treated with nutritional interventions such as enteral feeding. Methods: The PANCAX-1 (NCT02400398) prospective trial enrolled 31 cachectic advanced PDAC patients to receive jejunal tube peptide-based diet for 12 weeks who were planned for palliative chemotherapy. Out of 16 evaluable patients, 62.5% receiving enteral feeding met the primary endpoint of weight stability at 12 weeks. As part of an exploratory analysis of the PANCAX-1 trial, serial stool and blood samples were collected at 0 (C1D1), 6 (C2D1), and 12 (C3D1) weeks over the 12-week period of enteral feeding. Stool samples were analyzed using 16S v4 sequencing of the microbiome. Up to 219 plasma metabolites were analyzed by mass spectrometry and high-performance liquid chromatography. Results: A total of 29 stool samples were prospectively collected from 16 subjects with PDAC enrolled in PANCAX-1 who were evaluable for weight stability. Over 12 weeks of enteral feeding, statistically significant increases in the abundance of bacterial genera such as Veillonella (p=0.0150) and Actinomyces (p=0.0390) were observed, while there was a lower abundance of Bacteroides (p=0.0150) and Butyricicoccus (p=0.0390). Greater abundance of Veillonella and reduced Bifidobacterium at baseline were linked to greater weight stability. Plasma metabolomics in 10 subjects showed that weight unstable patients had significantly decreased levels of essential (L-histidine, L-phenylalanine) and non-essential amino acids (L-citrulline, L-tyrosine, all p<0.05) at the end of 12 weeks of enteral feeding. High stool Veillonella abundance was significantly associated with increases in the nucleotide 2-deoxycytidine 5-diphosphate and essential amino acid L-isoleucine but decreased TCA cycle metabolite alpha-ketoglutarate (all p<0.05). Conclusions: We are the first to demonstrate the feasibility of stool microbiome profiling and plasma metabolomics in paired stool and plasma samples from a prospective cohort of advanced PDAC patients on enteral feeding as their primary source of nutrition. Our findings are hypothesis-generating in that metabolites unique to weight stability and abundance of stool bacterial genera may inform future studies of anti-cachexia therapies involving enteral feeding or microbial modulation.

Inflorescence architecture underpins sexual reproduction in wild Musa species and productivity in edible banana cultivars. In a functional analysis we identified the apical inflorescence and lateral ‘cushion’ meristems and the change in flower type as the three primary components of inflorescence architecture. Five genotypes of two clone-sets of edible plantains (Musa AAB), were grown for four generations along an elevation gradient (1100 m to 2200 m, 16°C to 24°C) straddling the equator in the humid highlands of East Africa. The data consisted of peduncle length at harvest, fruit per hand (Fh) and hands per bunch (Hb). The activity of the apical inflorescence meristem drives peduncle length and lateral ‘cushion’ meristems determine fruit per hand. However, Hb is determined by a change in flower type – from fruit-forming to non-fruit forming. Site temperature affected Hb more than Fh, while development of the genet (rhizome) changed the allocation of resources between Hb and Fh, independently of the effect of site temperature. Clone-sets differed in their response to genet development. Cooler temperatures reduced the number of fruit-forming flowers in an inflorescence and changed the balance away from female towards male flowers. In banana breeding schemes, manipulating inflorescence components independently raises options for producing genotypes better suited to markets, environments, and cultural practices.

Recent expansion in data sharing has created unprecedented opportunities to explore structure-function linkages in ecosystems across spatial and temporal scales. However, characteristics of the same data product, such as resolution, can change over time or spatial locations, as protocols are adapted to new technology or conditions, which may impact the data’s potential utility and accuracy for addressing end user scientific questions. The National Ecological Observatory Network (NEON) provides data products for users from 81 sites and over a planned 30-year time frame, including discrete return Light Detection and Range (LiDAR) from an airborne observatory platform. LiDAR is a well-established and increasingly available remote sensing technology for measuring three-dimensional (3D) characteristics of ecosystem and landscape structure, including forest structural diversity. The LiDAR product that NEON provides can vary in point density from 2 – 25+ points/m² depending on instrument and acquisition date. We used NEON LiDAR from five forested sites to (1) identify the minimum point density at which structural diversity metrics can be robustly estimated across forested sites from different ecoclimatic zones in the USA and (2) to test the effects of variable point density on the estimation of a suite of structural diversity metrics and multivariate structural complexity types within and across forested sites. Twelve out of sixteen structural diversity metrics were sensitive to LiDAR point density in at least one of the five NEON forested sites. The minimum point density to reliably estimate the metrics ranged from 2.0 to 7.5 pt/m^2, but our results indicate that point densities above 7-8 pt/m² should provide robust measurements of structural diversity in forests for temporal or spatial comparisons. The delineation of multivariate structural complexity types from a suite of 16 structural diversity metrics was robust within sites and across forest types for a LiDAR point density of 4 pt/m² and above. This study shows that different metrics of structural diversity can vary in their sensitivity to the resolution of LiDAR data and users of these open-source data products should consider the point density of their data and use caution in metric selection when making spatial or temporal comparisons from these datasets.

Smoking during pregnancy remains one of the most significant risk factors for poor birth outcomes. The Loma Linda University Health Comprehensive Tobacco Treatment Program (CTTP) is the largest maternal tobacco cessation program in San Bernardino County – the largest county in the contiguous US. CTTP is an eight week, incentivized, behavioral intervention for tobacco cessation for pregnant smokers. As part of program evaluation, we used a retrospective cohort design to assess smoking abstinence and to identify predictors of relapse/smoking after enrollment. Among CTTP cohort enrollees (n=233) from 2012-2013 we found: 1) a 28.4% 8 week point prevalence abstinence (PPA), and at a median of 9 months of follow-up after the PPA, 81.6% continued to indicate tobacco cessation, and 2) a high rate of relapse or loss to follow-up (56%). Our modeling of relapse/smoking after enrollment indicated that this was higher in young mothers, non-Hispanic mothers (White, Black), first/third trimester mothers, and rural mothers. The evaluation identified efficacy of the behavioral model at 8 weeks, but that relapse/smoking was occurring in disparity populations. Formative research is needed to expand the programmatic outreach and enrollment of mothers wanting to quit smoking.

Abstract: This study evaluates the effect of paravertebral spinal injection (PSI), utilizing both subjective and objective assessments in chronic low back pain (LBP) associated with facet joint arthrosis over a one-month duration. Subjective questionnaires included the Visual Analogue Scale (VAS) for pain, Oswestry Disability Index, Health Survey SF-12, and the short Falls Efficacy Scale International (FES-I). Objective assessments included in-clinic gait and timed-up-and-go (TUG) tests using wearable sensors, as well as 48-hour daily physical activity (DPA) monitored using a chest-worn tri-axial accelerometer. Subjective and objective measures were performed prior to treatment, immediately after the treatment, and one-month afterthe treatment. Eight LBP patients were recruited for this study (mean age = 54±13 years, body mass index = 31.41±6.52 kg/m2, 50% males). Results show significant decrease in pain (~55%, p<0.05) and disability (Oswestry scores, ~21%, p<0.05). In-clinic gait and TUG were also significantly improved (~16% and ~18% faster walking and shorter TUG, p<0.05); however, DPA (including percentage of physical activities (walking and standing) and the number of steps) showed no significant change after PSI (p>0.25; effect size≤0.44). We hypothesize that DPA may continue to be truncated by conditioned fear-avoidance, a psychological state that may prevent increase in daily physical activity to avoid pain.

Periodontal ligament fibroblasts (PdLFs) exert important functions in oral tissue and bone remodeling following mechanical forces, which are specifically applied during orthodontic tooth movement (OTM). Located between the teeth and the alveolar bone, mechanical stress activates the mechanomodulatory functions of PdLFs including the regulation of local inflammation and activation of further bone-remodeling cells. Previous studies suggested the growth differentiation factor 15 (GDF15) as important pro-inflammatory regulator during the PdLFs mechanoresponse. However, the precise mechanism remains to be clarified, as GDF15 may act both intracrine and by receptor binding, potentially also in an autocrine manner. The extent to which PdLFs are susceptible to extracellular GDF15 has not yet been investigated. Thus, our study aims to examine the influence of GDF15 exposure on cellular properties of PdLFs and their mechanoresponse, which seems particularly relevant regarding disease- and aging-associated elevated GDF15 serum levels. Therefore, in addition to investigating potential GDF15 receptors, we analyzed its impact on proliferation, survival, senescence, and differentiation of human PdLFs, demonstrating a pro-osteogenic effect upon long-term stimulation. Furthermore, we detected an altered force-related inflammation and impaired osteoclast differentiation. Overall, our data suggest a major impact of extracellular GDF15 on PdLFs differentiation and their mechanoresponse.

The interrelationship between periodontal disease, obesity-related hyperlipidemia and mechanical forces as well as their modulating effects on the epigenetic profile of periodontal ligament (PdL) cells are assumed to be remarkably complex. The PdL serves as connective tissue between teeth and alveolar bone for pathogen defense and inflammatory response to mechanical stimuli occurring during tooth movement. Altered inflammatory signaling could promote root resorption and tooth loss. Hyperinflammatory COX2/PGE2 signaling was reported for human PdL fibroblasts (HPdLF) concomitantly stressed with P. gingivalis lipopolysaccharides and compressive force after exposure to palmitic acid (PA). The aim of this study was to investigate to what extent this is modulated by global and gene-specific changes in histone modifications. Quantitative expression of epigenetic key players and global H3Kac as well as H3K27me3 levels were evaluated in dual stressed HPdLF exposed to PA revealing a decreased force-related reduction in repressive H3K27me3. UNC1999-induced H3K27me3 inhibition reversed the hyperinflammatory response of dual-stressed PA-cultures characterized by COX2 expression, PGE2 secretion and THP1 adhesion. Reduced expression of the anti-inflammatory cytokine IL10 and increased association of H3K27me3 at its promoter-associated sites were reversed by inhibitor treatment. Thus, the data highlight an important epigenetic interplay between different stimuli to which the PdL is exposed.

The clinical characterization of small hepatocellular carcinoma (HCC) lesions in the liver and differentiation from heterogeneous inflammatory or fibrotic background is important for early detection and treatment. Metabolic monitoring of hyperpolarized ¹³C-labeled substrates has been suggested as a new avenue for diagnostic magnetic resonance. The metabolism of hyperpolarized [1-¹³C]pyruvate was monitored in mouse precision-cut liver slices (PCLS) of aged MDR2-KO mice, which served as a model for heterogeneous liver and HCC that develops similarly to the human disease. The relative in-cell activities of lactate dehydrogenase (LDH) to alanine transaminase (ALT) were found to be 0.40 ± 0.06 (n = 3) in healthy livers (from healthy mice), 0.90 ± 0.27 (n = 3) in heterogeneously inflamed liver, and 1.84 ± 0.46 (n = 3) in HCC. Thus, the in-cell LDH/ALT activities ratio was found to correlate with the progression of the disease. The results suggest that the LDH/ALT activities ratio may be useful in the assessment of liver disease. Because the technology used here is translational to both small liver samples that may be obtained from image-guided biopsy (i.e., ex vivo investigation) and to the intact liver (i.e., in a non-invasive MRI scan), these results may provide a path for differentiating heterogeneous liver from HCC in human subjects.

Background: Poor patient flow can lead to adverse outcomes for patients and organisational inefficiency. Many hospitals have addressed suboptimal patient flow by increasing resourcing, such as bed stock and staffing, however, this is an unsustainable approach. In determining the nature of poor patient flow issues, it is important to collect data from healthcare professionals who manage patient flow on a daily basis. Doing so provides insights into the current state of patient flow management in its entirety, whilst also helping with the development of sustainable solutions.; Methods: Thirteen semi-structured interviews were conducted with clinicians who were directly involved with patient flow at a tertiary care centre in Tasmania, Australia. Results: Through a thematic analysis method, four major themes were developed: managing patient flow, communication for decisions, tools as enablers and barriers and increasing complexity. Conclusions: The findings of this study provide great insights into patient flow issues, with potential solutions identified to address them.

The goal of classroom English instruction is to educate students on how to use the English language effectively for communication in any scenario. It is identified by presenting various teaching tactics and speaking activities to encourage students to participate more actively in conversations. The study intended to identify the problems in the speaking performance of Grade 8 Jade in Tagum City National High School. The study was conducted using a quantitative non-experimental descriptive survey method. Results revealed that the problems in speaking performance have garnered a mean of 3.20 (moderate) as descriptive equivalent and it was found out that the prevailing speaking problem is anxiety with a mean of 3.84, interpreted as high. Thus, an intervention program is designed to address the problems in the speaking performance of the respondents. This program is divided into two: Overcoming Speaking Anxiety Seminar-Workshop and Speaking Enhancement Activities.

Neurofilament light chain (Nf-L) is a well-known biomarker for axonal damage, however the corresponding circulating Nf-L analyte in CSF is poorly characterized. We, therefore, isolated new monoclonal antibodies against synthetic peptides, and these monoclonals were characterized for their specificity on brain-specific intermediate filament proteins. Two highly specific antibodies, ADx206 and ADx209, were analytically validated for CSF applications according to well-established criteria. Interestingly, using three different sources of purified Nf-L proteins, a significant impact on interpolated concentrations was observed. With a lower limit of analytical sensitivity of 100 pg/ml using bovine Nf-L as the calibrator, we were able to quantify the Nf-L analyte in each sample and these Nf-L concentrations were highly correlated to the Uman diagnostics assay (Spearman rho= 0.97, P<0.001). In the clinical diagnostic groups, the new Nf-L ELISA could discriminate patients with Alzheimer’s disease (AD, n=20) from frontotemporal lobe dementia (FTD, n=20) and control samples with subjective cognitive decline (SCD, n=20). Henceforth, this novel Nf-L ELISA with well-defined specificity and epitopes can be used to enhance our understanding of harmonizing the use of Nf-L as a clinically relevant marker for neurodegeneration in CSF.

Tick-borne encephalitis virus (TBEV) is a pathogenic, enveloped, positive-stranded RNA virus in the family Flaviviridae. Structural studies of flavivirus virions have primarily focused on mosquito-borne species with only one cryo-electron microscopy (cryo-EM) structure of a tick-borne species published. Here, we present a 3.3 Å cryo-EM structure of the TBEV virion of the Kuutsalo-14 isolate, confirming the overall organisation of the virus. We observe conformational switching of the peripheral and transmembrane helices of M protein, which can explain the quasi-equivalent packing of the viral proteins and highlights their importance in stabilizing the membrane protein arrangement in the virion. The residues responsible for the M protein inter-actions are highly conserved in TBEV but not in the structurally studied Hypr strain, nor in mosquito-borne flaviviruses. These interactions may compensate for the lower number of hydrogen bonds between E proteins in TBEV compared to the mosquito-borne flaviviruses. The structure reveals two lipids bound in the E protein, which are important for virus assembly. The lipid pockets are comparable to those recently described in mosquito-borne Zika, Spondweni, Dengue, and Usutu viruses. Our results thus advance the understanding of tick-borne flavivirus architecture and virion-stabilising interactions.

Mid-tropospheric cut-off low (COL) pressure systems are linked to severe weather, heavy rainfall and extreme cold conditions over South Africa. They often result in floods and snowfalls in winter disrupting economic activities. This paper examines the evolution and circulation patterns associated with severe COLs over South Africa. We evaluate the performance of the 4.4 km Unified Model (UM) which is currently used operationally by the South African Weather Service to simulate daily rainfall. Circulation variables and precipitation simulated by the UM were compared against ECMWF’s ERA Interim reanalyses and GPM precipitation at 24-hour timesteps. We present five recent (2016-2019) severe COLs that had high impact and found higher model skill when simulating heavy precipitation during the initial stages than the dissipating stages of the systems. A key finding was that the UM underestimated precipitation mainly due to inaccurate placing of COL centers and areas of heavy rainfall by up to 5° of latitude away from the actual location, due to the poor formulating of cumulus and microphysics schemes in the model. Understanding the performance and limitations of the UM model in simulating COL characteristics can benefit severe weather forecasting and contribute to disaster risk reduction in South Africa.

Gonorrhea is a major global public health problem with emergence of multiple drug-resistant strains with no effective vaccine. This retrospective cohort study aimed to estimate the effectiveness of the New Zealand meningococcal B vaccine against gonorrhea associated hospitalization. The cohort consisted of individuals born 1984-1999 residing in New Zealand, therefore eligible for meningococcal B vaccination during 2004-2008. Administrative datasets of demographics, customs, hospitalization, education, income tax and immunization, were linked using the national Integrated Data Infrastructure. The primary outcome was hospitalization with a primary diagnosis of gonorrhea. Cox’s proportional hazards models were applied with a Firth correction for rare outcomes to generate estimates of hazard ratios. Vaccine effectiveness estimates were calculated as 1-Hazard Ratio expressed as percent. There were 1,143,897 eligible cohort members, with 135 missing information on gender, 16,245 missing ethnicity and/or 197,502 missing deprivation hence 935,496 were included in the analysis. After adjustment for gender, ethnicity and deprivation, vaccine effectiveness (MeNZB™) against hospitalization caused by gonorrhea was estimated to be 24% (95% CI 1-42%). In conclusion, vaccination with MeNZB™ significantly reduced the rate of hospitalization from gonorrhea. This supports prior research indicating possible cross protection of this vaccine against gonorrhea acquisition and disease in the outpatient setting.

Canine atopic dermatitis (CAD) is a common chronic allergic skin disease. In our previous study, we isolated two probiotic strains, Lactococcus cremoris subsp. cremoris MP01 and Lacticaseibacillus paracasei subsp. paracasei MP02, from Mongolian fermented milk. These strains demonstrated potential in alleviating symptoms similar to AD and reducing specific immunoglobulin E (IgE) levels in a mouse model of AD. Building upon this discovery, our current investigation sought to evaluate the therapeutic potential of these probiotics for treating CAD. We conducted an open-label, single-arm clinical trial where dogs diagnosed with AD were administered LCP capsules containing Lc. cremoris subsp. cremoris MP01 and L. paracasei subsp. paracasei MP02 once daily for 60 days. Stool, skin swab, and venous blood specimens were collected at three intervals: before, and after 30 and 60 days of LCP intervention. The skin and fecal microbiomes were analyzed using full-length 16S rRNA sequencing. After 60 days of LCP intervention, notable improvements were observed in skin lesions and scratching behaviors, accompanied by reductions in both the Canine Atopic Dermatitis Extent and Severity Index (CADESI) and the Pruritus Visual Analogue Scale (PVAS) scores. Additionally, LCP intervention resulted in significant reductions in IgE levels and modulation in type 1 T helper (Th1)/ type 2 T helper cells (Th2)-related cytokine secretion. Microbiota analysis unveiled changes in the composition of both skin and gut microbiotas, including reductions in Shigella flexneri on the skin and Romboutsia in the gut. Levels of short-chain fatty acid (SCFA) increased following the 60-days of LCP intervention. These effects were likely mediated by alterations in gut microbiota and the upregulation of SCFA levels, which subsequently reduced the secretion of allergy-related IgE. Collectively, these mechanisms contributed to alleviating CAD symptoms, regulating skin microbiota composition, and reducing the adherence and invasion of environmental microbes and pathogens. Overall, our findings highlight the promising therapeutic potential of the Lc. cremoris subsp. cremoris MP01 and L. paracasei subsp. paracasei MP02 mixture as an effective strategy for managing CAD in dogs.

Mycobacterium tuberculosis variant bovis (MBO) has one of the widest known mammalian host ranges, including humans. Despite characterization of this pathogen in the 1800s, and whole genome sequencing of a UK strain (AF2122) nearly two decades ago, the basis of its host specificity and pathogenicity remains poorly understood. Recent experimental calf infection studies show that MBO strain Ravenel (MBO Ravenel) is attenuated in the cattle host. In the present study, experimental infections were performed to define attenuation and whole genome sequencing completed to identify regions of differences (RD) and single nucleotide polymorphisms (SNPs) to explain the observed attenuation. Comparative genomic analysis of MBO Ravenel against three pathogenic strains of MBO (strains AF2122-97, 10-7428 and 95-1315) was performed. Experimental infection studies on 5 calves each, with either MBO Ravenel or 95-1315, revealed no visible lesions in all 5 animals in the Ravenel group despite robust IFN-γ responses. Out of 486 polymorphisms in the present analysis, 173 were unique to MBO Ravenel among the strains compared. A high-confidence subset of 9 unique SNPs were missense mutations in genes with annotated functions impacting 2 major MBO survival and virulence pathways: 1) Cell wall synthesis & transport [espH (A103T), mmpL8 (V888I), aftB (H484Y), eccC5 (T507M), rpfB (E263G)], and 2) Lipid metabolism & respiration [mycP1(T125I), pks5 (G455S), fadD29 (N231S), fadE29 (V360G)]. These substitutions likely contribute to the observed attenuation. Results from experimental calf infections and the functional attributions of polymorphic loci on the genome of MBO Ravenel provide new insights into the strain’s genotype-disease phenotype associations.

Urban tree classification is pivotal in urban planning and management, facilitating informed decision-making processes. In this study, we introduce a novel data presentation method termed Pseudo Tree Crown, designed to enhance the accuracy and efficiency of urban tree classification. Leveraging the latest advancements in artificial intelligence (AI), we employ a state-of-the-art classification scheme, PyTorch, to maximize the accuracy of tree classification. Our results demonstrate a robust classification accuracy of over 95% from high spatial resolution imagery from Unmanned Aerial Vehicle (UAV), underscoring our proposed approach’s effectiveness. Moreover, the adaptability of our method renders it applicable to various study areas, highlighting its versatility and potential for widespread implementation in urban planning and management initiatives.

Drought occurrences in Rakai district take a strange model and it has been rampantly increasing causing reduced income levels for farmers, reduced farm yields, increased food insecurity and migration, wetland degradation, illness and loss of livestock. The purpose of this study was to investigate past and future characteristics of drought due to climate change in Rakai district. Datasets used include dynamically downscaled daily precipitation and temperature data from Coordinated Regional Climate Downscaling Experiment (CORDEX) at 0.44°×0.44° resolution over the Africa domain. R software (Climpact2 package), was used to generate SPI values, Mann Kendall trend test and Inverse Distance Weighting methods were used to examine temporal and spatial drought characteristics respectively. Results depicted more extreme and severe drought conditions for SPI12 under historical compared to SPI3,Kakuto, Kibanda and Lwanda sub counties were the most drought hot spot areas, positive trends of drought patterns for both time scales were observed, though only significant under SPI12. Projected results revealed extreme and severe drought conditions will be observed under RCP8.5 SPI12, and the least will be under RCP8.5 SPI3 and SPI12. Results further reveal that Kakuto, Kibanda, Kiziba, Kacheera, Kyalulangira, Ddwaniro and Lwanda sub counties will be the most drought hot spot sub counties across all time scales. Generally projected results reveals that the district will experience more drought conditions under RCP8.5 compared to RCP4.5 for time scale SPI12 and therefore urgent actions are needed.

Cardiac hypertrophy is an important and independent risk factor for the development of heart failure. To better understand the mechanisms and regulatory pathways involved in cardiac hypertrophy, there is a need for improved in vitro models. In this study, we investigated how hypertrophic stimulation affected human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs). The cells were stimulated with endothelin-1 (ET-1) for 8, 24, 48, 72, or 96h. Parameters including cell size, ANP-, proBNP-, and lactate concentration were analyzed. Moreover, transcriptional profiling using RNA-sequencing was performed to identify differentially expressed genes following ET-1 stimulation. The results show that the CMs increase in size by approximately 13% when exposed to ET-1 in parallel to increases in ANP and proBNP protein and mRNA levels. Furthermore, the lactate concentration in the media was significantly increased indicating that the CMs consume more glucose, a hallmark of cardiac hypertrophy. Using RNA-seq, a hypertrophic gene expression pattern was also observed in the stimulated CMs. Taken together, these results show that hiPSC-derived CMs stimulated with ET-1 display a hypertrophic response. The results from this study also provide new molecular insights about the underlying mechanisms of cardiac hypertrophy and may help accelerate the development of new drugs against this condition.

The study assessed the trapping efficacy of locally-modified 1) Gravid Aedes Trap(GAT) lined with insecticide-treated net (ITN) as a killing agent, 2) Autocidal Gravid Ovitrap(AGO) with sticky board in the semi-field system (SFS) and field setting. Fully-balanced Latin square experiments were conducted to compare GAT lined with ITN vs AGO, both with either yeast or grass infusion. Biogents-Sentinel (BGS) with BG-Lure and no CO2 was used as standard trap for Aedes mosquitoes. In the SFS, GAT outperformed AGO in collecting both nulliparous (65% vs 49%,OR=2.22,[95%CI:1.89-2.60],p

There is a strong anticipated future for human pluripotent stem cell-derived hepatocytes (hiPS-HEP), but so far their use has been limited due to insufficient functionality. We investigated the potential of hiPS-HEP as an in vitro model for metabolic diseases by combining transcriptomics with multiple functional assays. The transcriptomics analysis revealed that 86% of the genes were expressed at similar levels in hiPS-HEP as in human primary hepatocytes (hphep). Adult characteristics of the hiPS-HEP were confirmed by the presence of important hepatocyte features, e.g. Albumin secretion and expression of major drug metabolizing genes. Normal energy metabolism is crucial for modeling metabolic diseases, and both transcriptomics data and functional assays showed that hiPS-HEP were similar to hphep regarding uptake of glucose, LDL and fatty acids. Importantly, the inflammatory state of the hiPS-HEP was low under standard conditions, but in response to lipid accumulation and ER stress the inflammation marker TNFα was upregulated. Furthermore, hiPS-HEP could be co-cultured with primary hepatic stellate cells both in 2D and in 3D spheroids, paving the way for using these co-cultures for modeling NASH. Taken together, hiPS-HEP have the potential to serve as an in vitro model for metabolic diseases. Furthermore, differently expressed genes identified in this study can serve as targets for future improvements of the hiPS-HEP.

A two phase survey of epilepsy was conducted in selected villages in Mundri West and East Counties (26 June−8 July, 2021), an onchocerciasis-endemic area in Western Equatoria State in South Sudan. In the first phase, households were visited by a trained research team to identify persons suspected to have epilepsy. In the second phase, persons suspected to have epilepsy were interviewed and examined by a clinician to confirm the diagnosis. A total of 364 households agreed to participate in the survey, amounting to 2,588 individuals. The epilepsy screening questionnaire identified 91 (3.5%) persons suspected to have epilepsy, of whom in 86 (94.5%) the diagnosis of epilepsy was confirmed by a clinician. The overall prevalence of confirmed epilepsy was 3.3% (95% CI: 2.7-4.1%), and of nodding syndrome 0.9% (95% CI: 0.6-1.4%). In 61 (16.8%) households there was at least one person with epilepsy. Only 1,212 (46.9%) of 2,583 people took ivermectin during the last distribution round in 2021. The annual epilepsy incidence was 77.3/100.000 (95% CI: 9.4-278.9/100,000) and the annual epilepsy mortality 251.2/100,000 (95% CI: 133.8-428.7/100,000). In conclusion, a high prevalence and incidence of epilepsy was observed in villages in Mundri. Urgent action is needed to prevent children from developing onchocerciasis-associated epilepsy by strengthening the local onchocerciasis elimination programme.

Diet influences, and is influenced by, a wide range of socioeconomic, cultural, geographic, and genetic variables. Here we survey a matrix of such interactions as well as their connection to a variety of health outcomes, in a cohort of 689 diverse adults employed at Emory University and enrolled in the Center for Health Discovery and Well-Being (CHDWB) study. Principal component analysis (PCA) of the Block Food Frequency Questionnaire revealed seven PC cumulatively explaining 25.8% and each individually at least 2% of the proportional consumption of 110 food items. PC1 is strongly correlated with the Healthy Eating Index-2015 measure, and accordingly healthier scores associate with multiple measures of physical and mental health. It, as well as PC2 (likely a measure of food expense) and PC3 (carbohydrate versus protein consumption) show significant geographic structure across the Atlanta metropolitan area, correlating with race and ethnicity, income level, age and sex. Notably, a polygenic score for body mass index (BMI) consisting of 281 SNPs explains 2.8% of the variance in PC5, which is as strong as its association with BMI itself. PC5 appears to differentiate participants with respect to conscious eating behavior related to the choice of diet or comfort foods. Our analysis adds to the growing literature on factor analysis of socio-demographic influences on nutrition and health.

1) Background: Genomic medicine harbors the real potential to improve the health and healthcare jour-ney of patients, care provider experiences, and improve health system efficiency – even reducing health care costs. There is expected to be an exponential growth in medically necessary new genome- based tests and test approaches in coming years. Testing can also create scientific research and commercial opportu-nities beyond healthcare decision-making. The purpose of this research is to generate a better under-standing of Canada’s state of readiness for genomic medicine, and to provide some insights for other healthcare systems; (2) Methods: a mixed-methodsapproach of literature review and key informant in-terviews with a purposive sample of experts was used. Health system readiness was assessed using a pre-viously published set of conditions. (3) Results: Canada has created some of the established conditions but more needs to be done to improve the state of readiness for genome-based medicine. Important gaps are the need for linked information systems and data integration; evaluative processes that are timely, and transparent; navigational tools for care providers; dedicated funding to facilitate rapid onboarding and supports test development and proficiency testing; and broader engagement with a broader set of inno-vation stakeholders. These findings highlight the known role of organizational context, social influence, and other factors that are known to affect the diffusion of innovation within health systems

Opioids are highly addictive substances with a relapse rate of over 90%. While preclinical models of chronic opioid exposure exist for studying opioid dependence, none recapitulate the relapses observed in human opioid addiction. The mechanisms associated with opioid dependence, the accompanying withdrawal symptoms and the relapses that are often observed months or years after opioid dependence are poorly understood. Therefore, we developed a novel model of chronic opioid exposure whereby the level of administration is self-directed with periods of behavior acquisition, maintenance and then extinction alternating with reinstatement. This profile arguably mirrors that seen in humans, with initial opioid use followed by alternating periods of abstinence and relapse. Recent evidence suggests that dietary interventions that reduce inflammation, including omega-3 fatty acids such as docosahexaenoic acid (DHA), may reduce substance misuse liability. Using the self-directed intake model, we characterize the observed profile of opioid use and demonstrate that a diet enriched in polyunsaturated fat acids (PUFAs) ameliorates oxycodone-seeking behaviors in the absence of drug availability and reduces anxiety. Guided by the major role gut microbiota have on brain function, neuropathology, and anxiety, we profile the microbiome composition and the effects of chronic opioid exposure and DHA supplementation. We demonstrate that withdrawal of opioids led to a significant depletion in specific microbiota genera whereas DHA supplementation increased microbial richness, phylogenetic diversity, and evenness. Lastly, we examined the activation state of microglia in the striatum and found that DHA supplementation reduced the basal activation state of microglia. These preclinical data suggest that a diet enriched in PUFAs could be used as a treatment to alleviate anxiety induced opioid-seeking behavior and relapse in human opioid addiction.

The co-occurrence of depression and obesity has become a significant public health concern worldwide. Recent studies have shown that metabolic dysfunction, which is commonly observed in obese individuals and characterized by inflammation, insulin resistance, leptin resistance, and hypertension, is a critical risk factor for depression. This dysfunction may induce structural and functional changes in the brain, ultimately contributing to depression's development. Given that obesity and depression mutually increase each other's risk of development by 50-60%, there is a need for effective interventions that address both conditions. The comorbidity of depression with obesity and metabolic dysregulation is thought to be related to chronic low-grade inflammation, characterized by increased circulating levels of pro-inflammatory cytokines, and C-reactive protein (CRP). As pharmacotherapy fails in at least 30-40% of cases to adequately treat major depressive disorder, a nutritional approach is emerging as a promising alternative. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are a promising dietary intervention that can reduce inflammatory biomarkers, particularly in patients with high levels of inflammation, including pregnant women with gestational diabetes, patients with type 2 diabetes mellitus, and overweight individuals with major depressive disorder. Further effort directed to implement these strategies in clinical practice could contribute to improved outcomes in patients with depression and comorbid obesity and/or metabolic dysregulation.

The effect of the addition of fenugreek seed powder and Moringa oleifera leaf meal on the production performance and egg quality of Lohmann Brown laying hens was investigated. A total of 108 Lohmann-Brown layers, 48 weeks of age, were used and randomly assigned to six experimental groups of three replicates each in a randomized design. A control diet was supplemented with 3.6 g/hen/day of Moringa oleifera leaf meal and fenugreek seed powder alone or in various proportions as follows: control diet (T1), 100% Moringa oleifera leaf meal (T2), 25% fenugreek seed powder and 75% moringa oleifera leaf meal (T3), 50% fenugreek seed powder and 50% moringa oleifera leaf meal (T4), 75% fenugreek seed powder and 25% moringa oleifera leaf meal (T5) and 100% fenugreek seed powder (T6) were added on top of the control diet. Data were analyzed using one-way ANOVA by the general linear model method, using Tukey's multiple range tests to differentiate means. According to the results, fenugreek and moringa had a crude protein content of 25.17 and 27.8%, respectively. The groups administered T4 had significantly higher mean feed intake (120.75), feed conversion rate (2.315), egg production (77.22), and egg mass (52.08) than the others. Treatment 4 had a significant (P&lt;0.05) improvement in some egg quality traits such as shell weight, shell firmness, albumen weight, yolk weight, yolk color, and Haugh unit compared to the control. In summary, Treatment 4, a mixture of equal parts fenugreek seed powder and Moringa oleifera leaf meal, improved egg production performance and egg quality.

Loss of function of the hippocampus or frontal cortex is associated with reduced performance on memory tasks in which subjects are incidentally exposed to cues at specific places in the environment and are subsequently asked to recollect the location at which the cue was experienced. Here, we examined the roles of the rodent hippocampus and frontal cortex in cue-directed attention during encoding of memory for the location of a single incidentally experienced cue. During a spatial sensory preconditioning task, rats explored an elevated platform while an auditory cue was incidentally presented at one corner. The opposite corner acted as an unpaired control location. The rats demonstrated recollection of location by avoiding the paired corner after the auditory cue was in turn paired with shock. Damage to either the dorsal hippocampus or the frontal cortex impaired this memory ability. However, we also found that hippocampal lesions enhanced attention directed towards the cue during the encoding phase while frontal cortical lesions reduced cue-directed attention. These results suggest that the deficit in spatial sensory preconditioning caused by frontal cortical damage may be mediated by inattention to the location of cues during the latent encoding phase, while deficits following hippocampal damage must be related to other mechanisms such as generation of neural plasticity.

Standard of care for triple negative breast cancer (TNBC) involves the use of microtubule poisons like paclitaxel, which are proposed to work by inducing lethal levels of aneuploidy in tumor cells. While these drugs are initially effective in treating cancer, dose-limiting peripheral neuropathies are common. Unfortunately, patients often relapse with drug resistant tumors. Identifying agents against targets that limit aneuploidy may be a valuable approach for therapeutic development. One potential target is the microtubule depolymerizing kinesin, MCAK, which limits aneuploidy by regulating microtubule dynamics during mitosis. Using publicly available datasets, we found that MCAK is upregulated in triple negative breast cancer and is associated with poorer prognoses. Knockdown of MCAK in tumor-derived cell lines caused a two- to five-fold reduction in the IC50 for paclitaxel, without affecting normal cells. Using FRET and image-based assays, we screened compounds from the ChemBridge 50k library and discovered three putative MCAK inhibitors. These compounds reproduced the aneuploidy-inducing phenotype of MCAK loss, reduced clonogenic survival of TNBC cells regardless of taxane-resistance, and the most potent of the three, C4, sensitized TNBC cells to paclitaxel. Collectively, our work shows promise that MCAK may serve as both a biomarker of prognosis and as a therapeutic target.