Coronavirus disease 2019 restrictions impacted Canadians' daily living, especially those at higher risk of compromised health conditions. This study aimed to describe the physical, psychological, and social well-being of adults with disabilities, and older adults from May to June 2020. An online survey was used to administer standardized measures of mobility, anxiety and depression, boredom, resilience, technology readiness, social support, social networks, and participation. Seventy-two participants were recruited, with a mean age (SD) of 61.2 (13.8). 69.4% of participants had a disability, and 51.4% were older adults. 27.8% and 16.7% of participants exceeded the anxiety and depression cut-off scores, respectively. Boredom and restriction in participation were experienced by 76.4% and 80.1% of participants, respectively. Participants' mean (SD) resilience and life space scores were 72.4 (14.0) and 51.9 (24.0), respectively. Individuals with disabilities have comparatively higher mean anxiety (5.5 to 3.3), depression (4.8 to 2.9), and boredom (92.2 to 72.3) scores than those without. Individuals with a disability had lower resilience (69.9 to 78.0) and felt more life space restrictions (45.4 to 67.6). Our findings revealed issues with anxiety, boredom, participation, and life space activity. This information may provide supporting evidence when creating policies to mitigate existent health and social inequities.

The neurodegenerative diseases (Alzheimers, Parkinsons, amyotrophic lateral sclerosis, Huntingdons) and the prion disorders, have in common a dysregulation of metalloprotein chemistry involving redox metals (Cu,Fe,Mn). The consequent oxidative stress gives rise to protein plaques and neuronal cell death. An equilibrium exists between the functional requirement of the brain for Cu and Fe and their destructive potential with the production of reactive oxygen species. The importance of the brain barrier is highlighted in regulating the import of these metals. Upregulation of key transporters occurs in foetal and neonatal life when brain metal requirement is high and is down-regulated in adult life when need is minimal. By contrast a neonatal mode of CTR1 upregulation persists in feral N.Ronaldsay sheep. This has led to the premise that metal regulation may return to the default setting in ageing with implications for neurodegenerative disease.

Peanut hulls (PH) are an edible food waste that is an underutilized food source for human consumption. While edible and palatable, they are mainly diverted to livestock feed or building materials. Here, we describe existing literature on human food valorization of PHs and propose methods to optimize recapturing nutrients (e.g. protein, fiber, polyphenols) lost by treating PHs as waste. Incorporated into common foods, PHs can be processed into functional ingredients to improve nutrient-density and the corresponding positive health outcomes associated with increases in plant foods. PH valorization can also address additional priorities of the UN Sustainable Development Goals using a Food Systems Approach (FSA) including food waste, increasing economic opportunities for farmers, and increasing the availability of healthy shelf-stable foodstuffs to address food security. Recent advances in sustainable food processing technologies can be utilized to safely incorporate peanut hulls into human food streams. We propose future applications that could make meaningful impacts to food availability and the nutritional composition of common foods. While the limited literature on this topic spans several decades, no global operations exist to incorporate peanut hulls and most publications precede the technological ‘green revolution’. The approaches outlined in this review may help bolster commercialization of this underutilized and nutritious food potentially improving opportunities for multiple global stakeholders.

Disordered eating is a serious health concern globally. The etiology is complex and multidimensional and differs somewhat for each specific eating disorder. Several risk factors have been identified which include psychological, genetic, biochemical, environmental, and sociocultural factors. Poor body image, low self-esteem, teasing, family dynamics, and exposure to media images have also been identified as risk factors. While it is enticing to consider a single behavioral risk factor, doing so fails to consider the documented environmental, social, psychological, biological, and cultural factors that contribute to the development of an eating disorder in a multidimensional and complex integration that is undoubtedly unique to everyone. Focusing only on any one factor without taking the complex etiology into account is remiss. For example, it has been suggested that the use of dietary supplements may lead to eating disorders, despite a lack of evidence to support this conjecture. Therefore, the purpose of this review is to examine the evidence-based risk factors for eating disorders and discuss why connecting dietary supplements to eating disorder etiology is not supported by the scientific literature and may interfere with treatment. Established, effective prevention and treatment approaches for eating disorders should be the focus of public health initiatives in this domain.

Clinical work conducted over the last seventeen years at the EEG Institute in Los Angeles and by other neurofeedback providers around the world has demonstrated the utility of extending frequency-based neurofeedback deep into the infra-low frequency (ILF) region, using the method of endogenous neuromodulation described herein. The method is characterized by the absence of any overt reinforcements, which makes it possible to extend the clinical reach to extremely low frequencies. As the training frequency is lowered, the signal becomes more difficult to discriminate, and ultimately it can only be discerned by the brain itself, in the process of endogenous neuromodulation. The method emulates how the brain does skill learning in general: It must observe itself performing the skill, with feedback on its performance. While the immediate target of ILF neurofeedback is enhanced self-regulatory competence--with symptomatic relief and functional recovery the secondary consequences, progressive lowering of the target frequencies has led to improved outcomes in application to challenging dysfunctions such as episodic suicidality, migraine, seizures, and bipolar mood swings. The work has also yielded insights into how the frequency domain is organized. The training proceeds best at frequencies that are specific to each individual, and these are referred to as optimal response frequencies (ORFs). These frequencies differ for various placements but stand in two fixed relationships to one another, one that holds over the EEG spectral range, and another that holds over the entire ILF range. Training in the ILF region engages the dynamics of the glial-neuronal networks, which govern tonic, resting state regulation. The collective clinical experience with ILF neuromodulation within a large practitioner network supports the case for making protocol-based, individualized ‘homeodynamic’ regulation a therapeutic priority, particularly for our most impacted clinical populations: addiction, trauma formations, traumatic brain injury, and the dementias. The case is made for further outcome studies and foundational research.

The aim of this study was to assess if the ovine articular cartilage serine proteinase inhibitors (SPIs) were related to the Kunitz inter-α-trypsin inhibitor (ITI) family. Ovine articular cartilage was finely diced and extracted in 6M urea and SPIs isolated by sequential anion exchange, HA affinity and Sephadex G100 gel permeation chromatography. Selected samples were also subjected to chymotrypsin and concanavalin-A affinity chromatography. Eluant fractions from these isolation steps were monitored for protein and trypsin inhibitory activity and pooled fractions assessed by affinity blotting using biotinylated trypsin to detect active SPIs and by Western blotting using antibodies to α1-microglobulin, bikunin, TSG-6 and 2-B-6 (+) CS stub epitope generated by chondroitinase-ABC digestion. This identified 2-B-6 (+) positive 220-250,120, 58 and 36 kDa SPIs. The 58 kDa SPI contained α1-microglobulin, bikunin and chondroitin-4-sulphate stub epitope consistent with its identity as the α1-microglobulin-bikunin (AMBP) precursor and was also isolated by concanavalin-A lectin affinity chromatography indicating it had N-glycosylation. Kunitz protease inhibitor (KPI) species of 36, 26, 12 and 6 kDa could be autolytically generated by prolonged storage of the aforementioned 120 and 58 kDa SPIs; chymotrypsin affinity chromatography also generated the 6kDa SPI. KPI domain 1 and 2 SPIs were separated by concanavalin lectin affinity chromatography, domain 1 displayed affinity for this lectin indicating it had N-glycosylation. KPI 1 and 2 both displayed potent inhibitory activity towards trypsin, chymotrypsin, kallikrein, leucocyte elastase and cathepsin G. Localisation of versican, lubricin and HA in the surface regions of articular cartilage represented probable binding sites for the ITI SPs with likely importance in the preservation of joint function.

The Sustainable Development Goals provide a global development agenda that is meant to be inclusive of all people. However, the development needs for vulnerable populations such as youth are not reflected within the policy agenda of some developing countries. One of the reasons for this is that research that explores health and wellbeing concerns for young people are sparse in the region and where they exist, the focus has been on marginalized subgroups. To address this gap, this cross-sectional study explored the health and wellbeing of youth in Kenya. We conducted 10 focus group discussions and 13 in-depth interviews with youth ages 15 to 24 years. A thematic analysis of the data revealed that structural factors are important influencers of youth perceptions and their social constructions of health and wellbeing. Kenyan youth are concerned about the health status and healthcare services in their communities, as well as issues of community trust of youths and perceived risks of political misuse and emotional suffering. Our findings suggest that youth transitioning into adulthood in resource constrained areas experience feelings of being powerless and unable to take charge over their own life. This impacts how they perceive and socially construct health and wellbeing.

Untargeted and targeted approaches are the traditional metabolomics workflows acquired for a wider understanding of the metabolome under focus. Both approaches have their strengths and weaknesses. The untargeted, for example, is maximizing the detection and accurate identification of thousands of metabolites, while the targeted is maximizing the linear dynamic range and quantification sensitivity. These workflows, however, are acquired separately, so researchers compromise either a low-accuracy overview of total molecular changes (i.e., untargeted analysis) or a detailed yet blinkered snapshot of a selected group of metabolites (i.e., targeted analysis) by selecting one of the workflows over the other. In this review, we present a novel single injection simultaneous quantitation and discovery (SQUAD) metabolomics that combines targeted and untargeted workflows. It is used to identify and accurately quantify a targeted set of metabolites. It also allows data retro-mining to look for global metabolic changes that were not part of the original focus. This offers a way to strike the balance between targeted and untargeted approaches in one single experiment and address the two’s limitations. This simultaneous acquisition of hypothesis-led and discovery-led datasets allows scientists to gain more knowledge about biological systems in a single experiment.

Decision support systems based on machine learning models should be able to help users identify opportunities and threats. Popular model-agnostic explanation models can identify factors that support various predictions, answering questions like “What factors affect sales?” or “Why did sales decline?”, but do not highlight what a person should or could do to get a more desirable outcome. Counterfactual explanation approaches address intervention, and some even consider feasibility, but there has been no evaluation of their suitability for real-time applications, such as question answering. Here we address this gap by introducing a novel model-agnostic method that provides specific, feasible changes that would impact the outcomes of a complex black-box AI model for a given instance and assess its real-world utility by measuring its real-time performance and ability to find achievable changes. The method uses the instance of concern to generate high-precision explanations and then applies a secondary method to find minimally contrastive and maximally probable high-precision counterfactual explanations, while limiting contrasted features to changes that are achievable. We demonstrate that using this method, it is possible to find such explanations quickly enough for use in real-time systems. High-precision achievable minimally contrastive explanations would be useful in applications where people seek remedial actions or question how effective a proposed remedy is likely to be.

While traditionally people relinquish their pets to an animal shelter or pound, the internet provides a newer method to re-home. We analysed advertisements (ads) on the largest website in Australia for trading dogs and cats, gumtree.com.au. Data was collected in 2016. Dogs were sampled on February 7, 16 and 24, 2016 and cats on February 9, 19 and 26, 2016 with 2640 ads for relinquished dogs, and 2093 ads for relinquished cats. It was estimated >31,000 puppies/dogs and >24,000 kittens/cats are relinquished on gumtree.com.au per year. The median age of dogs was 1.42 and cats 0.9 years of age. There were 23% of dog ads and 62% of cat ads for free animals. Compared to the human population there were proportionately more ads in Queensland and fewer ads in Victoria. A total of 15 people were surveyed who had relinquished a dog or cat using gumtree.com.au. The dog owners used gumtree.com.au because they believed the shelters were full (n = 4), and; they wanted to see/interview the new owner (n = 2). For cat owners it was because they had originally got the cat on gumtree.com.au (n = 2); they use gumtree.com.au for other things, and it works (n = 2), and; they wanted to see/interview the new owner (n = 2). The data collected will be valuable for implementation of policy and interventions to protect the welfare of un-wanted dogs and cats.

In many countries, governments have implemented non-pharmaceutical techniques to limit COVID-19 transmission. Restricting human mobility is one of the most common interventions, including lockdown, travel restrictions, working from home, etc. However, due to the strong transmission ability of the virus variants, further rounds of interventions, including a strict lockdown, are not considered as effective as expected. The paper aims to understand how the lockdown policy and pandemics changed human mobility in the real scenario. Here we focus on understanding the mobility changes caused by compliance with restrictions and risk perceptions, using the mobility index from the Google report during three strict lockdown periods in Leeds, the largest city in the county of West Yorkshire, England from March 2020 to March 2021. The research proposed the time-varying z-scores and Principal Component Analysis (PCA) to simulate how local people dynamically process and perceive health risk based on multi-dimensional daily COVID-19 reports first. Further modelling highlights exponentially increasing policy non-compliance through the duration of lockdown, probably attributable to factors such as mental anxiety and economic pressures. Finally, the proposed nonlinear regression model examines the mobility changes caused by the population's dynamic risk perceptions and lockdown duration. The case study at Leeds fits data well and shows that the third lockdown policy took effect much slower than the first. At the same time, the negative impact of the epidemic on population mobility decayed 40% in the third lockdown period in contrast with the first lockdown. The risk perception estimation methods could reflect that the local population became increasingly accustomed to the COVID-19 situation, and local people rationally evaluated the risks of COVID in the third lockdown period. The results prove that simulated risk perceptions and policy decay could explain urban mobility behaviour during the mobility well during lockdown periods, which could be a reference for future decision-making processes.

Teachers of English as a foreign language in Taiwan are challenged to organize multi-dimensional language activities for foreign students coming from ASEAN countries, including Japan, the Philippines, South Korea, and Vietnam. With different cultural backgrounds, these students have different prior knowledge of Taiwanese culture, and, because of the similarities and differences between Taiwan and these countries, it is meaningful to explore the development of globalization with the students, who are learning both English and Chinese. The different historical backgrounds, various cultural and religious differences, and social conditions, such as gender relationships in working places, are significant topics for class discussions. When teachers serve as discussion facilitators, they encourage students to express their own multi-identities and expectations for the exchange program. Most interesting of all is to find out about their own short-term and long-term career goals. 32 foreign students from the Philippines and Vietnam were recruited for research. Questionnaires were used to assess their foreign language learning motivation and strategies, as well as to discover the learning environment they prefer and their globalization prospects. It was found that multi-lingual language policies for promoting globalization in higher education are very likely to influence the success of foreign student study in Taiwan.

Rising temperatures due to the climate change can significantly impact the frost/thaw condition of airport pavements in cold regions. This case study investigates the implications of the the warming temperatures on frost/thaw penetration and frost-heave of pavements for critical airports across Canada. To this end, different methods were used in the quantification process through climate change simulations considering the emission scenario RCP8.5 in a 20- and 40-year time horizon. The results show that climate change would have different design implications for airport pavements depending on their location. The predictions suggest a shallower frost penetration depth and possibly less frost-heave for the airports not underlain by permafrost, while airports over permafrost areas might experience an increase in thickness of the active layer ranging from 41 to 57 percent by 2061. Among the different methods used in this study, it was observed that some methods performed the best in predicting frost depth of fine soils, while others worked better with the frost depth prediction of coarse soils. The results indicate the need for more mechanistic models to provide a more realistic prediction of frost/thaw penetration as compared to the existing empirical models.

Dissolved calcium (Ca2+) concentrations in freshwater ecosystems are of growing concern as increasing levels have been implicated in altering the environmental conditions and biodiversity. Elevated Ca2+ levels and sporadic re-emergence and disappearance of invasive zebra mussels in Kentucky Lake in recent years served as a motivation for this study. The objective of this study was to determine Ca2+ spatial and temporal patterns in Kentucky Lake, selected tributary streams, and the Ohio River during and following a zebra mussel invasion. Over 1000 water samples were collected and analysed for dissolved calcium during 2018-2022. Approved analytical methods were followed for sampling and measuring dissolved calcium levels. Results revealed significant spatial and temporal patterns. Kentucky Lake Ca2+ levels varied between 15-25 mg/L depending on the sampling location and month/year. Kentucky Lake channel sites exhibited comparably higher concentrations of Ca 2+ than did most embayment and/or stream sites, indicating that tributary streams did not serve as primary sources of calcium to the lake. Dissolved calcium levels at main lake sites exceeded the threshold for zebra mussel growth and reproduction in 2018 during the time when zebra mussels were present. Calcium in lake water samples collected from 2019 through 2022 was at or just below the threshold. Temporal trend data showed a gradual increase in Ca2+ in Kentucky Lake throughout the study period but remaining at or below the threshold level considered critical for the zebra mussels’ reproduction and development. Calcium levels in the Ohio River site at Paducah were similar to Kentucky Lake reflecting the predominance of Tennessee River water, while levels at the Brookport site were consistent with values known to support zebra mussel populations. The elevated calcium levels in Kentucky Lake waters during the late winter and early spring months may be due to natural sources (mineral weathering) as well as human activities in the Tennessee River basin. This study emphasizes the need for continued calcium monitoring in the watershed to determine the potential for future zebra mussel outbreaks and potential influences on the lake ecosystem and its functions.

Background: Producing, distributing or discussing child sexual abuse materials (CSAM) is often committed through the dark web in order to remain hidden from search engines and regular users. Additionally, on the dark web, the CSAM creators employ various techniques to avoid detection and conceal their activities. The large volume of CSAM on the dark web presents a global social problem and poses a significant challenge for helplines, hotlines and law enforcement agencies. Objective: Identifying CSAM discussions on the dark web and uncovering associated metadata insights into characteristics, behaviours and motivation of CSAM creators. Participants and Setting: We have conducted an analysis of more than 353,000 posts generated by 35,400 distinct users and written in 118 different languages across eight dark web forums in 2022. Out of these, approximately 221,000 posts were written in English and contributed by around 29,500 unique users. Method: We propose a CSAM detection intelligence system. The system uses a manually labelled dataset to train, evaluate and select an efficient CSAM classification model. Once we identify CSAM creators and victims through CSAM posts on the dark web, we proceed to analyze, visualize and uncover information concerning the behaviors of CSAM creators and victims. Result: The CSAM classifier, based on Support Vector Machine model, exhibited good performance, achieving the highest precision of 92.3\%, accuracy of 87.6\% and recall of 84.2\%. Its prediction time is fast, taking only 0.3 milliseconds to process a single post on our laptop. While, the Naive Bayes combination is the best in term of recall, achieving 89\%, and its prediction time is just 0.1 microseconds per post. Across the eight forums in 2022, our Support Vector Machine model detected around 63,000 English CSAM posts and identified near 10,500 English CSAM creators. The analysis of metadata of CSAM posts revealed meaningful information about CSAM creators and their victims, such as: (1) the ages and nationalities of the victims typically mentioned by CSAM creators, (2) forum topics where the CSAM creators assign their posts, and (3) online platforms preferred by CSAM creators for sharing or uploading CSAM. Conclusion: Our CSAM detection system exhibits high performance in precision, recall, and accuracy in real-time when classifying CSAM and non-CSAM posts. Additionally, it can extract and visualize valuable and unique insights about CSAM creators and victims by employing advanced statistical methods. These insights prove beneficial to our partners, i.e. national hotlines and child agencies.

Child sexual abuse inflicts lifelong devastating consequences for victims and is an ongoing social concern. In most countries, child sexual abuse material (CSAM) distribution is illegal. As a result, there are many research papers in the literature which proposed technologies to detect and investigate CSAM. In this survey, a comprehensive search of the peer-reviewed journal and conference paper databases (including preprints) is conducted to identify high-quality literature. We use the PRISMA methodology to refine our search space to 2,761 papers published by Springer, Elsevier, IEEE and ACM. After iterative reviews of title, abstract and full text for relevance to our topics, 43 papers are included for full review. Our paper provides a comprehensive synthesis of the tasks of the current research and how the papers use techniques and datasets to solve their tasks and evaluate their models. To the best of our knowledge, we are the first to focus exclusively on online CSAM detection and prevention with no geographic boundaries, and the first survey to review papers published after 2018. It can be used by researchers to identify gaps in knowledge and relevant publicly available datasets that may be useful for their research.

Plant-based diets are increasingly popular for health as well as financial, ethical, and religious reasons. The medical literature clearly demonstrates that plant-based diets can be both nutritionally sufficient and medically beneficial. However, any person on an intentionally restrictive but poorly-informed diet may predispose themselves to clinically-relevant nutritional deficiencies. For persons on a poorly-informed plant-based diet, deficiencies are possible in both macronutrients (protein, essential fatty acids) and micronutrients (vitamin B12, iron, calcium, zinc and vitamin D). Practitioner evaluation of symptomatic patients on a plant-based diet requires special consideration of 7 key nutrient concerns for plant-based diets. This article translates these concerns into 7 practical questions that all practitioners can introduce into their patient assessments and clinical reasoning. Ideally, persons on plant-based diets should be able to answer these 7 questions. Each serves as a heuristic prompt for both clinician and patient attentiveness to a complete diet. As such, these 7 questions support increased patient nutrition knowledge and practitioner capacity to counsel, refer, and appropriately focus clinical resources.

Background and aims: Despite recent advances in advanced prostate cancer treatments, there are no clinically useful biomarkers or treatments for men with such cancers. Targeted therapies have shown promise, but there remain fewer actionable targets in prostate cancer than in other cancers. This work aims to characterize BRD9, currently understudied in prostate cancer, and investigate its co-expression with other genes to assess its potential as a biomarker and therapeutic target in human prostate cancer. Materials and methods: Omics data from a total of 2053 prostate cancer patients across 11 independent datasets were accessed via Cancertool and cBioPortal. mRNA expression and co-expression, mutations, amplifications, and deletions were assessed with respect to key clinical parameters including survival, Gleason grade, stage, progression and treatment. Network and pathway analysis was carried out using Genemania, and heatmaps were constructed using Morpheus. Results: BRD9 is overexpressed in prostate cancer patients, especially those with metastatic disease. BRD9 expression did not differ in patients treated with second generation antiandrogens versus those who were not. BRD9 is co-expressed with many genes in the SWI/SNF and BET complexes, as well as those in common signaling pathways in prostate cancer. Summary and conclusions: BRD9 has potential as a diagnostic and prognostic biomarker in prostate cancer. BRD9 also shows promise as a therapeutic target, particularly in advanced prostate cancer, and as a co-target alongside other genes in the SWI/SNF and BET complexes, and those in common prostate cancer signalling pathways. These promising results highlight the need for wider experimental inhibition and co-targeted inhibition of BRD9 in vitro and in vivo, to build on the limited inhibition data available.

Single crystals of quaternary adamantine type Cu•GaGeS4 were grown by chemical vapor transport technique using iodine as transport agent. Dark red transparent crystals grew in a temperature gradient of dT = 900–750 °C. Chemical characterization by X-ray fluorescence showed an off-stoichiometric composition of the Cu•GaGeS4 crystals, in particular a slight Ge-deficit. By X-ray diffraction, Cu•GaGeS4 was found to adopt the chalcopyrite-type structure with the space group I-42d. The cation distribution in this structure was analyzed by multiple energy anomalous synchrotron X-ray diffraction and it was found that Cu and vacancies occupy the 4a site, whereas Ga and Ge occupy the 4b site. The band gap energies of several off-stoichiometric Cu•GaGeS4 crystals were determined by UV-Vis spectroscopy and are in the range of 2.1 to 2.4 eV. A non-linear correlation of the band gap energy with the Ge-content of the compound follows the usual bowing behaviour of semiconductor alloys with a bowing parameter of b = 1.45(0.08).

Consumption guidelines are a common way to improve conscious consumption behaviors in areas where game fish are known to contain contaminants. However, guideline information can be difficult to distribute, and effectiveness difficult to measure. To increase the distribution and effectiveness of guideline information for the Detroit River, an educational campaign was launched in 2010, which included distribution of pamphlets with consumption information, posting of permanent signs at popular fishing locations, and hiring River Walkers to personally communicate with anglers. In 2013 and 2015, we conducted in-person surveys of active shoreline anglers to determine the effectiveness of education and outreach efforts. Results from the survey indicated that 55% of anglers were aware of the guidelines in 2013, and by 2015 36% had communicated the information to family or friends. However, anglers were often unwilling to reduce consumption of popular game species, despite high contaminant levels. Encouragingly, black anglers were most likely to supplement their diet with species lower in contaminants. Our results suggest that utilizing multiple educational strategies including reaching out directly to individual anglers may improve conscious consumption behavior among the targeted population, providing a template for educational campaigns to successfully target vulnerable populations.

With rising rates of human obesity, the study aimed to determine the relationship between maternal diet-induced obesity and offspring morphometrics and behaviour in mice. Pregnant and lactating female mice fed a diet high in fat and sugar (HFHS) commonly consumed by human populations showed decreased food, calorie, and protein intake but increased adiposity at the expense of lean mass. The pre-weaning body weight of HFHS offspring was reduced for the first postnatal week but not thereafter with HFHS female offspring having higher body weights by weaning, due to continuing higher fractional growth rates. Post-weaning, there were minor differences in offspring food and protein intake. Maternal diet, however, affected fractional growth rate and total body fat content of male but not female HFHS offspring. Maternal diet did not affect offspring locomotor activity or social behaviour in either sex. Both male and female HFHS offspring displayed reduced anxiety-related behaviours with sex differences in particular aspects of the elevated plus maze task. In the novel object recognition task, performance was impaired in male but not female HFHS offspring. Collectively, the findings demonstrate that maternal obesity alters the growth, adiposity, and behaviour of male and female offspring, with sex-specific differences.

Large ruminant production is associated with high greenhouse gas emissions (GHGe) intensity, with the highest in southeast Asia being Laos at 102.9 CO2eq/kg meat produced, compared with average global meat emissions intensity of 33 CO2eq/kg. As recent studies in Laos identified emissions control molasses blocks (ECBs) achieved abatement of 470kg CO2eq/20kg block consumed, a study was conducted with a supplement mix with reported methane reducing properties, containing plant tannins and citral extract, salt, molasses and water. Groups of housed dairy buffalo (n=7) and pasture-fed grazing beef cows (n=11) were randomly selected, body condition scores estimated (BCS:1-5) and baseline nasa-oral methane eructation measured daily for 2 weeks. All animals were offered 300-400g/day of the mix for a month, with buffalo accessing abundant fresh cut forages whereas the grazing cows accessing rice straw and pasture declining in quality and quantity due to severe drought. The buffalo consumed all of the mix and retained their BCS of 3, whereas the cattle consumed between 200-300g/day of the mix and their BCS declined from 1.5 to 1.0 during the trial. Analysis of data points (buffalo n=309; cattle n=378) found average methane concentration (AMP) per animal of both cohorts increased over the 2 week baseline period, then declined during the supplementation period by 36% in the buffalo and 18% in cattle cohorts.

Covalent DNA protein crosslinks (DPCs) are common lesions that block replication. We examine here the consequence of DPCs on mutagenesis involving replicational template-switch reactions in Escherichia coli. 5-azacytidine (5azaC) is a potent mutagen for template-switching, dependent on DNA cytosine methylase (Dcm), implicating the trapped Dcm-DNA covalent complex as the initiator for mutagenesis. The leading strand of replication is more mutable than the lagging strand, explained by blocks to the replicative helicase and/or fork regression. We find that template-switch mutagenesis induced by 5-azaC does not require DSB repair via RecABCD. The ability to induce the SOS response is anti-mutagenic by an unknown mechanism. Mutants in recB, but not recA, exhibit high constitutive rates of template-switching and we suggest that RecBCD-mediated DNA degradation prevents template-switching associated with fork regression. A mutation in the DnaB fork helicase also promotes high levels of template-switching. We also find that other DPC-inducers, formaldehyde (a non-specific crosslinker) and ciprofloxacin (a topoisomerase II poison) are also strong mutagens for template-switching. Induction of mutations and genetic rearrangements that occur by template-switching may constitute a previously unrecognized component of the genotoxicity and genetic instability promoted by DPCs.

Purpose: A number of imaging readout schemes have been proposed for renal arterial spin labelling (ASL) to quantify kidney cortex perfusion, including gradient echo based methods of balanced fast field echo (bFFE) and gradient-echo echo-planar imaging (GE-EPI), or spin echo based schemes of spin-echo echo planar imaging (SE-EPI) and turbo spin-echo (TSE). Here, we compare these imaging schemes to evaluate the optimal imaging scheme for pulsed ASL (PASL) assessment of human kidney cortex perfusion at 3 T. Methods: Ten healthy volunteers with normal renal function were scanned using each 2D multislice imaging scheme, in combination with a respiratory triggered FAIR (flow-sensitive alternating inversion recovery) ASL scheme on a 3 T Philips Achieva scanner. All volunteers returned for a second identical scan session within two weeks of the first scan session. Comparisons were made between the imaging schemes in terms of perfusion weighted image (PWI) signal-to-noise ratio (SNR) and perfusion quantification, temporal SNR (tSNR), spatial coverage, and repeatability. Results: For each imaging scheme, renal cortex perfusion was calculated (bFFE: 276 ± 29 mL/100 g/min, GE-EPI: 222 ± 18 mL/100 g/min, SE-EPI: 201 ± 36 mL/100 g/min, TSE: 200 ± 20 mL/100 g/min). Perfusion was found to be higher for GE based readouts compared to SE based readouts, with significantly higher measured perfusion for the bFFE readout compared to all other schemes (P < 0.05), attributed to the greater vascular signal present. Despite the PWI-SNR being significantly lower for SE-EPI compared to all other schemes (P < 0.05), the SE-EPI readout gave the highest tSNR and was found to be the most reproducible scheme for the assessment of kidney cortex, with a CoV of 17.2%, whilst minimizing variability of the perfusion weighted signal across slices for whole kidney perfusion assessment. Conclusion: For the assessment of kidney cortex perfusion, SE-EPI provides optimal tSNR, minimal variability across slices and repeatable data acquired in a short scan time with low specific absorption rate.

Reduced inhibitory glycinergic neurotransmission is implicated in a number of neurological conditions such as neuropathic pain, schizophrenia, epilepsy and hyperekplexia. Restoring glycinergic signalling may be an effective method of treating these pathologies. Glycine transporters (GlyTs) control synaptic and extra-synaptic glycine concentrations and slowing the reuptake of glycine using specific GlyT inhibitors will increase glycine extracellular concentrations and increase glycine receptor (GlyR) activation. Glycinergic neurotransmission can also be improved through positive allosteric modulation (PAM) of GlyRs. Despite efforts to manipulate this synapse, no therapeutics currently target it. We propose that dual action modulators of both GlyTs and GlyRs may show greater therapeutic potential than those targeting individual proteins. To show this, we have characterized a co-expression system in Xenopus laevis oocytes consisting of GlyT1 or GlyT2 co-expressed with GlyRα1. We use two electrode voltage clamp recording techniques to measure the impact of GlyTs on GlyRs and the effects of modulators of these proteins. We show that increases in GlyT density in close proximity to GlyRs diminish receptor currents. Reductions in GlyR mediated currents are not observed when non-transportable GlyR agonists are applied or when Na+ is not available. GlyTs reduce glycine concentrations across different concentration ranges, corresponding with their ion-coupling stoichiometry, and full receptor currents can be restored when GlyTs are blocked with selective inhibitors. We show that partial inhibition of GlyT2 and modest GlyRα1 potentiation using a dual action compound, is as useful in restoring GlyR currents as a full and potent single target GlyT2 inhibitor or single target GlyRα1 PAM.

Objectives: This paper presents a statistical review of modelling simulations for frequency and sensitivity of COVID-19 testing paradigms. Methods: We performed a review of preprints and published articles on PubMed from January 1, 2020 – March 1, 2021 using the search terms “COVID screening testing”, “COVID testing frequency”, “COVID testing frequency screening” and “SARS-CoV-2 testing frequency”.Results: Several authors’ conclusions support the claim that test frequency and test sensitivity both play a role in reducing SARS-CoV-2 transmission. We highlight the interplay between frequency of testing, test sensitivity and the speed at which test results are available in our review. Conclusions: Evidence suggests that sensitivity and frequency of testing both play a part in decreasing transmission of disease. We conclude that, overall, test sensitivity plays less of a role in reducing disease transmission in a population compared to the frequency of testing and how quickly test results are available.

With a longer-term goal of addressing the comparative behavior of the aqueous halides F$^-$, Cl$^-$, Br$^-$, and I$^-$ on the basis of quasi-chemical theory (QCT), here we study structures and free energies of hydration clusters for those anions. We confirm that energetically optimal $(\mathrm{H_2O})_n\mathrm{X}$ clusters, with X = Cl$^-$, Br$^-$, and I$^-$, exhibit \emph{surface} hydration structures. Computed free energies based on optimized surface hydration structures utilizing a harmonic approximation, typically (but not always) disagree with experimental free energies. To remedy the harmonic approximation, we utilize single-point electronic structure calculations on cluster geometries sampled from an AIMD (\emph{ab initio} molecular dynamics) simulation stream. This \emph{rough-landscape} procedure is broadly satisfactory and suggests unfavorable ligand crowding as the physical effect corrected. Nevertheless, this procedure can break down when $n \gtrsim 4$, with the characteristic discrepancy resulting from a relaxed definition of clustering in the identification of $(\mathrm{H_2O})_n\mathrm{X}$ clusters, including ramified structures natural in \emph{physical cluster theories.} With ramified structures, the central equation for the present rough-landscape approach can acquire some inconsistency. Extension of these physical cluster theories in the direction of QCT should remedy that issue, and should be the next step in this research direction.

There is a major clinical need for accurate biomarkers for prostate cancer prognosis, to better inform treatment strategies and disease monitoring. Current clinically recognised prognostic factors, including prostate-specific antigen (PSA) levels, lack sensitivity and specificity in distinguishing aggressive from indolent disease, particularly in patients with localised intermediate grade prostate cancer. There has therefore been a major focus on identifying molecular biomarkers that can add prognostic value to existing markers, including investigation of DNA methylation, which has a known role in tumorigenesis. In this review, we will provide a comprehensive overview of the current state of DNA methylation biomarker studies in prostate cancer prognosis, and highlight the advances that have been made in this field. We cover the numerous studies into well-established candidate genes, and explore the technological transition that has enabled hypothesis-free genome-wide studies and the subsequent discovery of novel prognostic genes.

The COVID-19 pandemic was associated with increases in some healthcare-associated infections. We investigated the impact of the pandemic on rates and molecular epidemiology of Clostridioides difficile infection (CDI) within one VA Hospital. We anticipated that the potential widespread use of antibiotics for pneumonia during the pandemic might increase CDI rates given that antibiotics are a major risk for CDI. Hospital data on patients with CDI and recurrent CDI (rCDI) were reviewed pre-COVID-19 pandemic (2015 to 2019) and during the pandemic (2020 - 2021). Restriction endonuclease analysis (REA) strain typing was performed on CD isolates recovered from stool samples collected from 10/2019 – 3/2022. CDI case numbers declined 43.2% in 2020 – 2021 compared to the annual mean over the previous 5 years. Stool test positivity rate was also lower during the COVID-19 pandemic (14.3% vs. 17.2%; P = 0.013). Although inpatient volume declined, rates of CDI among inpatients were reduced by 34.2% in 2020 – 2021. Mean monthly cases of rCDI also declined significantly after 2020 [3.38 (95% CI: 2.89 – 3.87) vs. 1.92 (95% CI: 1.27 – 2.56); P = &lt;0.01]. Prior to the pandemic, REA group Y was the most prevalent CD strain among the major REA groups (27.3%). During the first wave of the pandemic from March 8, 2020, through June 30, 2020, there was an increase in the relative incidence of REA group BI (26.7% vs. 9.1%. After adjusting for CDI risk factors, a multivariable logistic regression model revealed that odds of developing an REA group BI CDI increased during the first pandemic wave (OR 6.41, 95% CI: 1.03 – 39.91) compared to the pre-pandemic period. In conclusion, the incidence of CDI and rCDI decreased significantly during the initial waves of the COVID-19 pandemic. In contrast, REA BI (Ribotype 027), a virulent, previously epidemic CD strain and frequently associated with hospital transmission and outbreaks, reappeared as a prevalent strain during the first wave of the pandemic.

Improvement of agronomic traits in crops through gene editing (GE) relies on efficient trans-formation protocols for delivering the CRISPR/Cas9-coded transgenes. Recently, a few embryo-genesis-related genes have been described, the co-delivery of which significantly increases the transformation efficiency with reduced genotype dependency. Here we characterized the trans-genic and GE events in wheat (cv. Fielder) when transformed with the GROWTH-REGULATING FACTOR 4 (GRF4) and its cofactor GRF-INTERACTING FACTOR 1 (GIF1) chimeric gene. Trans-formation efficiency in our experiments ranged from 22% to 68%, and the editing events were faithfully propagated into the following generation. Both low and high copy number integration events were recovered in the T0 population with the various level of integrity of the left and right T-DNA borders. We also generated a population of wheat plants with ten different gRNAs targeting 30 loci in the genome. Comparison of the epigenetic profiles at the target sites and editing efficiency revealed a significant positive correlation between chromatin accessibility and muta-genesis rate. Overall, preliminary screening of the transgene quality and GE events in the T0 population of plants regenerated through the co-delivery of GRF-GIF can allow for the propagation of the best candidates for further phenotypic analysis.

The oral mucosa represents a defense between the external environment and the rest of the body and encompasses several antimicrobial and antiviral mechanisms. Oral mucosal cells are constantly bathed in hypotonic saliva (normally one-third tonicity compared to plasma) and are repeatedly exposed to environmental stresses of tonicity, temperature and pH by the drinks we imbibe (e.g. hypotonic: water, tea, coffee; hypertonic: assorted fruit juices, red wines), as well as of diverse microbial and viral flora. In the mouth, the broad-spectrum antiviral mediator MxA (a dynamin-family large GTPase) is constitutively expressed in healthy periodontal tissues, and also induced by Type III interferons (e.g. IFN-λ1). Endogenously induced human MxA and exogenously expressed human GFP-MxA formed membraneless biomolecular condensates in the cytoplasm of oral carcinoma cells (OECM1 cell line). These condensates likely represent storage granules in equilibrium with antivirally active dispersed MxA. Remarkably, cytoplasmic MxA condensates were exquisitely sensitive sensors of hypotonicity – the condensates in oral epithelium disassembled within 1-2 min of exposure of cells to saliva-like one-third hypotonicity, and spontaneously reassembled in the next 4-7 min. OECM1 cells preloaded with calcein-AM (a reporter of cytosolic “macromolecular crowding”) confirmed unquenching and then requenching of calcein fluorescence during this process. Hypertonicity had little effect on MxA condensates. The spontaneous reassembly of GFP-MxA condensates in oral epithelial cells even under continuous saliva-like hypotonicity was slowed by the protein phosphatase inhibitor cyclosporin A (CsA) and by the K-channel blocker tetraethylammonium chloride (TEA) suggestive of the involvement of the volume-sensitive WNK kinase-protein phosphatase (PTP)-K-Cl cotransporter (KCC) pathway in the regulated volume decrease (RVD) during condensate reassembly in oral cells. Thus, physiologically, hypotonic drinks (water, tea, coffee) trigger a rapid deployment of antiviral MxA throughout the cytoplasm of oral epithelial cells, with subsequent salvage of MxA back into storage granules/condensates.

Background: During the COVID-19 pandemic some family physicians were overburdened and experienced difficulties reaching vulnerable patients and meeting the increased need for psycho-social support. This randomized controlled trial (RCT) tested whether a primary healthcare (PHC) based community health worker (CHW) intervention could tackle psychosocial suffering due to physical distancing measures in patients with limited social networks. Methods: CHWs provided 8 weeks of tailored psychosocial support to the intervention group. Control group patients received ‘care as usual’. The impact on feelings of emotional support, social isolation, social participation, anxiety and fear of COVID-19 were measured longitudinally using a face-to-face survey to determine their mean change from baseline. Self-rated change in psychosocial health at 8 weeks was determined. Results: We failed to find a significant effect of the intervention on the prespecified psychosocial health measures. However, the intervention did lead to significant improvement in self-rated change in psychosocial health. Conclusions: This study confirms partially the existing evidence on the effectiveness of CHW in-terventions as a strategy to address mental health in PHC in a COVID context. Further research is needed to elaborate the implementation of CHWs in PHC to reach vulnerable populations during and after health crises.

The ubiquitin proteasome system (UPS) utilizes an orchestrated enzymatic cascade of E1, E2, and E3 ligases to add single or multiple ubiquitin-like molecules as post-translational modification (PTM) to proteins. Ubiquitination can alter protein functions and/ or marks ubiquitinated proteins for proteasomal degradation but deubiquitinases (DUBs) can reverse protein ubiquitination. While the importance of DUBs as regulatory factors in the UPS is undisputed, many questions remain on DUB selectivity for protein targeting, their mechanism of action, and the impact of DUBs on the regulation of diverse biological processes. Furthermore, little is known about the expression and role of DUBs in tumors of the human central nervous system (CNS). In this comprehensive review, we have used publicly available transcriptional datasets to determine the gene expression profiles of 99 deubiquitinases (DUBs) from five major DUB families in seven primary pediatric and adult CNS tumor entities. Our analysis identified selected DUBs as potential new functional players and biomarkers with prognostic value in specific subtypes of primary CNS tumors. Collectively, our analysis highlights an emerging role for DUBs in regulating CNS tumor cell biology and offers a rationale for future therapeutic targeting of DUBs in CNS tumors.

The field of microbial pathogenesis seeks to identify the agents and mechanisms responsible for disease causation. Since Robert Koch introduced postulates that were used to guide the characterization of microbial pathogens, technological advances have substantially increased the capacity to rapidly identify a causative infectious agent. Research efforts currently focus on causation at the molecular level with a search for virulence factors (VFs) that contribute to different stages of the infectious process. We note that the quest to identify and characterize VFs sometimes lacks scientific rigor, and this suggests a need to examine the epistemology of VF characterization. We took this premise as an opportunity to explore the epistemology of VF characterization. In this perspective, we discuss how the characterization of various gene products that evolved to facilitate bacterial survival in the broader environment have potentially been prematurely mischaracterized as VFs that contribute to pathogenesis in the context of human biology. Examples of the reasoning that can affect misinterpretation, or at least premature assignment of mechanistic causation, are provided. Our aim is to refine categorization of VFs by emphasizing a broader biological view of their origin.

Children and adolescents with severe burns require dressing changes, associated with pain. As immersive virtual reality (VR) gained prominence as non-pharmacological adjuvant analgesia, we conducted a systematic review and meta-analysis on the efficacy of full immersive VR on pain experienced during dressing changes in hospitalized children and adolescents with severe burns. This exercise included quality and risk of bias assessment. The systematic reviewsearch resulted in eight studies and 142 patients. This exercise included quality and risk of bias assessment. Due to missing data, four studies were excluded from the meta-analysis. Fixed effects meta-analysis of the four included studies (n = 104) revealed a large effect size (ES) (SMD=0.94; 95% CI=0.62, 1.27; Z=5.70; p&lt;0.00001) for adjuvant full immersive VR compared to standard care. In conclusion, adjuvant full immersive VR significantly reduces pain experienced during dressing changes in children and adolescents with burns. We therefore recommend implementing full immersive VR as an adjuvant in this specific setting and population. However, this requires further research into the hygienic use of VR appliances in health institutions. Furthermore, due to the high cost of the hardware, a cost-benefit analysis is required. Finally, research should also verify the long term physical and psychological benefits of VR.

The improved understanding of the underlying mechanisms of oxidative damage and/or chronic diseases is of high priority in dietary research. Although the chemical extraction of biofunctional molecules from different fruits and cereals have been studied extensively, the impact of food processing and digestion on bioactivity has not been studied systematically. The aim of this study was to investigate the biofunctional potential of blackcurrant powder incorporated into wholemeal wheat and barley cookies in after simulated in vitro digestion. The incorporation of blackcurrant significantly (p<0.05) increased the total phenolic content (about 60 %), significantly improved oxygen radical absorbance capacity (about 25 %) of the cookie digesta. Additionally cellular antioxidant and anti-proliferative activity (lowest EC₅₀ value 1.02 mg/mL) on human liver cancer cell model, HepG2 was significantly enhanced. Bioactive metabolites of blackcurrant incorporated cookies were significantly supressed the inflammatory cytokine genes IL-1β (about 3-fold), IL-6 (about 0.5-fold) and NF-kB (about 2-fold) regulation and upregulated satiety gene NUCB-2/Nesfatin-1 (about 5-fold) compare with wholemeal wheat and barley control cookies. The exerted synergistic effects of this study suggest that there may be a new and effective option to prevent and control chronic diseases in human.

Oil spills from offshore drilling and coastal refineries often cause degradation of coastal wetlands that can take a long time to recover. Early oil detection may prevent losses and speed up recovery if monitoring of the initial oil extent, oil impact, and recovery are in place. Satellite imagery data can provide a cost-effective alternative to expensive airborne imagery or labor intensive field campaigns for monitoring effects of oil spills on wetlands. However, these satellite data may be restricted in their ability to detect and map ecosystem recovery post-spill given their spectral measurement properties and temporal frequency. In this study, we assessed whether spatial and spectral resolution, and other sensor characteristics influence the ability to detect and map vegetation stress and die-off due to oil. We compared how well three satellite multispectral sensors: WorldView2, RapidEye and Landsat EMT+, match the ability of the airborne hyperspectral AVIRIS sensor to map oil-induced vegetation stress, recovery, and die-off after the DeepWater Horizon oil spill in the Gulf of Mexico in 2010. We found that finer spatial resolution (3.5m) provided better delineation of the oil-impacted wetlands and better detection of vegetation stress along oiled shorelines in saltmarsh wetland ecosystems. As spatial resolution become coarser (3.5m to 30m) the ability to accurately detect and map stressed vegetation decreased. Spectral resolution did improve the detection and mapping of oil-impacted wetlands but less strongly than spatial resolution, suggesting that broad-band data may be sufficient to detect and map oil-impacted wetlands. AVIRIS narrow-band data performs better detecting vegetation stress, followed by WorldView2, RapidEye and then Landsat 15m (pan sharpened) data. Higher quality sensor optics and higher signal-to-noise ratio (SNR) may also improve detection and mapping of oil-impacted wetlands; we found that resampled coarser resolution AVIRIS data with higher SNR performed better than either of the three satellite sensors. The ability to acquire imagery during certain times (midday, low tide, etc.) or a certain date is also important in these tidal wetlands; WorldView2 imagery captured at high-tide detected a narrower band of shoreline affected by oil likely because some of the impacted wetland was below the tideline. These results suggest that while multispectral data may be sufficient for detecting the extent of oil-impacted wetlands, high spectral and spatial resolution, high-quality sensor characteristics, and the ability to control time of image acquisition may improve assessment and monitoring of vegetation stress and recovery post oil spills.

Background: Using the COM-B model as a framework, an EU-wide survey aimed to ascertain multidisciplinary healthcare workers’ (HCWs) knowledge, attitudes and behaviours on antibiotics, antibiotic use and antibiotic resistance. The UK findings are presented. Methods: A 43-item questionnaire was developed through a two-round modified Delphi consensus process. The UK target quota was 1,315 respondents. Results: 2,404 participants responded. The highest proportion were nursing and midwifery professionals (42%), pharmacists (23%) and medical doctors (18%). HCWs correctly answered that antibiotics are not effective against viruses (97%), they have associated side effects (97%), unnecessary use makes antibiotics ineffective (97%) and healthy people can carry antibiotic resistant bacteria (90%). However, fewer than 80% correctly answered that using antibiotics increases a patient’s risk of antimicrobial resistant infection or that resistant bacteria can spread from person to person. Whilst the majority of HCWs (81%) agreed there is a connection between their antibiotic prescribing behaviour and the spread of antibiotic resistant bacteria, only 64% felt that they have a key role in controlling antibiotic resistance. The top three barriers to providing advice or resources were lack of resources (19%), insufficient time (11%) and the patient being uninterested in the information (7%). Approximately 35% of UK respondents who were prescribers prescribed an antibiotic at least once in the last week due to fear of patient deterioration or complications. Conclusion: These findings highlight that a multifaceted approach to tackling the barriers to prudent antibiotic use in the UK is required and provides evidence for guiding targeted policy, intervention development and future research. Education and training should focus on patient communication, information on spreading resistant bacteria and increased risk for individuals.

We investigated how Artificial Intelligence (AI) reveals factors shaping COVID-19 vaccine hesitancy among healthcare providers by examining their open-text comments. We conducted a longitudinal survey starting in spring of 2020 with 38,788 current and former female nurses in three national cohorts to assess how the pandemic has affected their livelihood. In January and March-April 2021 surveys, participants were invited to contribute open-text comments and answer specific questions about COVID-19 vaccine uptake. A closed-ended question in the survey identified vaccine-hesitant (VH) participants who either had no intention or were unsure of receiving a COVID-19 vaccine. We collected 1,970 comments from VH participants and trained two Machine Learning (ML) algorithms to identify behavioral factors related to VH. The first predictive model classified each comment into one of three Health Belief Model (HBM) constructs (barriers, severity, and susceptibility) related to adopting disease prevention activities. The second predictive model used the words in January comments to predict the vaccine status of VH in March-April 2021; vaccine status was correctly predicted 89% of the time. Our results showed that 35% of VH participants cited barriers, 17% severity, and 7% susceptibility to receiving a COVID-19 vaccine. Out of the HBM constructs, the VH participants citing a barrier, such as allergic reactions and side effects, had the most associated change in vaccine status from VH to later receiving a vaccine.

Indigenous forests cover 24% of New Zealand and provide valuable ecosystem services. However, a national map of forest types, that is, physiognomic types, which would benefit conservation management, does not currently exist at an appropriate level of detail. While traditional forest classification approaches from remote sensing data are based on spectral information alone, the joint use of space-based optical imagery and structural information from synthetic aperture radar (SAR) and canopy metrics from air-borne Light Detection and Ranging (LiDAR) facilitates more detailed and accurate classifications of forest structure. We present a support vector machine (SVM) classification using data from ESA’s Sentinel-1 and 2 missions, ALOS PALSAR, and airborne LiDAR to produce a regional map of physiognomic types of indigenous forest in New Zealand. A five-fold cross-validation of ground data showed that the highest classification accuracy of 80.9% is achieved for bands 2, 3, 4, 5, 8, 11, and 12 from Sentinel-2, the ratio of bands VH and VV from Sentinel-1, HH from PALSAR, and mean canopy height and 97th percentile canopy height from LiDAR. The classification based on the optical bands alone was 73.1% accurate and the addition of structural metrics from SAR and LiDAR increased accuracy by 7.8%. The classification accuracy is sufficient for many management applications for indigenous forest in New Zealand, including biodiversity management, carbon inventory, pest control, ungulate management, and disease management. National application of the method will be possible in several years, once national LiDAR coverage is achieved, and a national canopy height model is available.

Rapidly providing a definitive diagnostic test that can be used broadly by healthcare providers and members of the public in the setting of a disease emergency is critical to limit pathogen spread, develop and deploy medical countermeasures, and mitigate the social and economic harms of a serious epidemic or pandemic. There is extraordinary expertise within and outside of government working on these issues, and major accomplishments have been made to accelerate test development, expand laboratory testing capacity, and establish widespread point-of-care testing. Still, the United States does not have a plan to rapidly respond, to develop, manufacture, or deploy at national scale diagnostic testing in the earliest days of a new infectious disease crisis. Nor does the nation have a plan to sustain testing capacity at high volume over the course ofan enduring epidemic or pandemic. To address this gap, we are proposing a National Diagnostics Action Plan that describes the steps that are urgently needed to prepare for future infectious disease emergencies, as well as the actions we must take at the first signs of such events. These recommendations require substantial collaboration between the US government (USG) and the private sector to solve a series of challenges now, as well as to prepare for the massive and rapid scale-up of laboratory and point-of-care test development and testing capacity in future emergencies. The recommendations include establishing pre-event contracts; ensuring rapid access to clinical samples; creating a permanent public-private testing coordinating body to allow for rapid information sharing and improved cooperation among the USG, test developers, and clinical laboratories; and accelerating testing rollout at the beginning of an event—andthus, the effective public health management of a disease crisis. These recommendations were informed by extensive discussion with people who managed the COVID-19 and monkeypox responses, review of past reports written on diagnostic challenges, and the experiences of the authors.

Dietary patterns established during adolescence might play a role in adulthood disease. We examined the stability of dietary patterns (DPs) from childhood through adolescence and into young adulthood (from age 8 to 34 years). Data from 130 participants (53 females) of Saskatchewan Pediatric Bone Mineral Accrual Study (aged 8-15 years, at baseline) were included. Multiple 24-hour recalls were collected annually from 1991 to 1997, 2002 to 2005 and 2010 and 2011. Using principal component analysis, “Vegetarian-style”, “Western-like”, “High-fat, high-protein”, “Mixed” and “Snack” DPs were derived at baseline. Applied DP scores for all annual measurements were calculated using factor loading of baseline DPs and energy-adjusted food group intakes. We analyzed data using generalized estimating equations. The tracking coefficient represents correlation between baseline dietary pattern scores and all other follow-up dietary pattern scores. We found a moderate tracking for the “Vegetarian-style” (ß=0.44, P<0.001) and “High-fat, high-protein” (ß=0.39, P<0.001) DPs in females and “Vegetarian-style” DP (ß=0.30, P<0.001) in males. Remaining DPs showed a poor-to-fair tracking in both sexes. No tracking for “Western-like” DP in females was observed. Assessing overall change in DP scores from childhood to young adulthood showed an increasing trend in adherence to “Vegetarian-style” DP and decreasing trend in adherence to “High-fat, high-protein” DP by age in both sexes (P<0.001). While “Western-like” and “Mixed” DP scores increased only in males (P<0.001). These findings suggest that healthy dietary habits established during childhood and adolescence moderately continue into adulthood.

Young people living with perinatal infections of Human Immunodeficiency Virus (YLPHIV) face a chronic disease, with treatment including adherence to life-long antiretroviral treatment (ART). The aim of this QES was to explore adherence to ART for YLPHIV as an assemblage within the framework of the BPS model with a new materialist perspective. We searched up to November 2021 and followed the ENTREQ and Cochrane guidelines for QES. All screening, data extraction and critical appraisal was done in duplicate. We analysed and interpreted the findings innovatively, by creating images of meaning, a storyboard, and storylines. We then reported the findings in a narrative first person story. We included 47 studies and identified 9 storylines. We found that treatment adherence has less to do with humans’ preferences, motivations, needs and dispositions, and more to do with how bodies, viruses, things, ideas, institutions, environments, social processes, and social structures assemble. This QES highlights that adherence to ART for YLPHIV is a multisensorial experience in a multi agentic world. Future research into rethinking the linear and casual inferences we are accustomed too in evidence-based health care is needed if we are to adopt multidisciplinary approaches to address pressing issues such as adherence to ART.

Lactic acid bacteria are traditionally applied in a variety of fermented food products and have the capability to produce a wide range of bioactive ingredients during fermentation including vitamins, bacteriocins, bioactive peptides and bioactive compounds. The bioactivity and health benefits associated with these ingredients have gained interest in applications in the functional dairy market and have relevance both as components produced in situ and as functional additives. This review provides a brief description of the regulations regarding the functional food market in the European Union as well as an overview of some of the functional dairy products currently available in the Irish and European markets. A better understanding of the production of these ingredients excreted by lactic acid bacteria can further drive the development and innovation of the continuously growing functional food market.

The recent rise of deep learning (DL) and its promising capabilities in capturing non-explicit detail from large datasets have attracted substantial research attention in the field of medical image processing. DL provides ground for technology development for computer-aided diagnosis and segmentation in radiology and radiation oncology. Amongst the anatomical locations where recent auto-segmentation algorithms have been employed, the pelvis remains one of the most challenging due to large intra- and inter-patient soft-tissue variabilities. This review provides a comprehensive and clinically-oriented overview of DL-based segmentation studies for bladder, prostate, cervical and rectal cancers, highlighting the key findings, challenges and limitations.

This study aims to explore the associations between pediatric adverse events (PAEs) and hospital and patient characteristics within the inpatient hospital setting, focusing solely on the framework of pediatric quality indicators (PDIs) from the Agency for Healthcare Research and Quality (AHRQ). Specifically, the study focuses on NQI 03 Neonatal Blood Stream Infection (NBSI). The analysis utilizes discharge data from the Healthcare Cost and Utilization Project (HCUP) Kids’ Inpatient Databases (KID) for the year 2019. Through this analysis, the study seeks to answer research questions regarding associations between hospital characteristics and patient characteristics with NQI 03. The methodology employs bivariate and multivariate logistic regression models to analyze patient-level encounters of NBSI. The results indicate that smaller, rural, and non-teaching hospitals exhibit significantly lower odds of NQI 03 compared to large hospitals. Various individual factors such as gender, age, race, service lines, payment sources, and major operating room procedures also demonstrate differing levels of significance in relation to NQI 03, warranting further investigation. This study provides contextual expansion on the findings and offers valuable insights into PAEs in the inpatient hospital setting, specifically focusing on NBSI within the PDIs framework. It highlights areas for developing evidence-based interventions and guidelines for clinicians and policymakers. Ultimately, the findings contribute to the growing understanding of factors influencing NBSI and emphasize the importance of targeted strategies for improving pediatric patient safety.

Background: Radiotherapy plays an important role in the management and survival of patients with breast cancer. The aim of this study was to examine the association between age, comorbidities and use of radiotherapy in this population. Methods: Patients diagnosed with breast cancer from 2004–2013 were identified from the American College of Surgeons National Cancer Database (NCDB). Follow-up time was measured from the date of diagnosis (baseline) to the date of death or censoring. Adjusted hazard ratios (aHR) and 95% confidence intervals (95%CI) were used as the measure of association. Results: Independently of comorbidities and other important outcome-related factors, patients >65 years of age who received radiotherapy survived significantly longer than those who did not receive radiotherapy (aHR = 0.53, 95%CI = 0.52–0.54). However, as women aged, those with comorbidities were less likely to receive RT (adjusted P-trend by age <0.0001). Conclusions: The development of decision-making tools to assist clinicians, and older women with breast cancer and comorbidities, are needed to facilitate personalized treatment plans regarding RT. This is particularly relevant as the population ages and the number of women with breast cancer is expected to increase in the near future.

The tiered laboratory framework for HIV viral load monitoring accommodates a range of HIV viral load testing platforms, with quality assessment critical to ensure quality patient testing. HIV plasma viral load testing is challenged by the instability of viral RNA. An approach using an RNA stabilizing buffer is described for the Xpert® HIV-1 Viral Load (Cepheid) assay and was tested in remote laboratories in South Africa. EDTA-plasma panels with known HIV viral titres were prepared in PrimeStore molecular transport medium for per-module verification and per-instrument external quality assessment. The panels were transported at ambient temperatures to 13 testing laboratories during 2017 and 2018, tested according to standard procedures and uploaded to a web portal for analysis. A total of 275 quality assessment specimens (57 verification panels and two EQA cycles) were tested. All participating laboratories met study verification criteria (n=171 specimens) with an overall concordance correlation coefficient (ρ_c) of 0.997 (95% confidence interval [CI]: 0.996 to 0.998) and a mean bias of -0.019 log cp/mL (95% CI: -0.044 to 0.063). The overall EQA ρ_c (n=104 specimens) was 0.999 (95% CI: 0.998 to 0.999), with a mean bias of 0.03 log cp/mL (95% CI: 0.02 to 0.05). These panels are suitable for use in quality monitoring of Xpert® HIV-1 VL and are applicable to laboratories in remote settings.

The temperature of the indoor environment is important for health and wellbeing especially at the extremes of age. The study aim was to undertsand the relationship between self-reported thermal sensation and extremity skin temperature in care home residents with and without dementia. The Abbreviated Mental Test (AMT) was used to discriminate residents to two categories, those with and those without dementia. After acclimatisation, measurements included: tympanic membrane temperature, thermal sensation rating followed by infrared thermal mapping of non-dominant hand and forearm. Sixty-nine afebrile adults (60-101 years of age) were studied in groups of two to five, in mean ambient temperatures of 21.4^oC-26.6^oC (median 23.6^oC). Significant differences were observed between groups; thermal sensation rating (p=0.02), tympanic temperature (p=0.01), fingertip skin temperature (p=0.01) and temperature gradients; fingertip-wrist p=0.001 and fingertip-distal forearm, p=0.001.

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.

Insecticides with novel modes of action are required to complement the pyrethroids currently relied upon for controlling malaria vectors. One example of this is the neonicotinoid clothianidin, which is found in SumiShield™ 50WG used in indoor residual spraying (IRS). In a preliminary experiment, mortality in insecticide susceptible and resistant An. gambiae adults exposed to SumiShield™ 50WG-treated filter papers reached 80% by 3-days post-exposure and 100% by 6-days post-exposure. Next, cement, wood, and mud tiles were treated with SumiShield™ 50WG or K-Othrine® WG250 (deltamethrin IRS formulation) and insecticide resistant and susceptible Anopheles and Aedes were exposed to these surfaces periodically for up to 18-months. Pyrethroid resistant Cx. quinquefasciatus were also exposed at 9 months. Between exposures tiles were stored in heat and relative humidity conditions reflecting those found in the field. On these surfaces, SumiShield™ 50WG was effective at killing both susceptible and resistant An. gambiae for 18 months post-treatment, while mortality amongst the resistant strains when exposed to deltamethrin (K-Othrine® WG250) IRS was not above that of the negative control. Greater efficacy of SumiShield™ 50WG was also demonstrated against insecticide resistant strains of An. funestus compared to deltamethrin, though the potency was lower when compared with An. gambiae. In general, a higher efficacy of SumiShield™ 50WG was observed on cement and mud compared to wood. SumiShield™ 50WG demonstrated poor residual activity against Aedes aegypti and Culex quinquefasciatus. Overall, the results suggest SumiShield™ 50WG is well suited for malaria control.

Summary Genome assembly projects have grown exponentially due to breakthroughs in sequencing technologies and assembly algorithms. Evaluating the quality of genome assemblies is critical to ensure the reliability of downstream analysis and interpretation. To fulfil this task, we have developed the AssemblyQC pipeline that performs file-format validation, contaminant checking, contiguity measurement, gene- and repeat-space completeness quantification, telomere inspection, taxonomic assignment, synteny alignment, scaffold examination through Hi-C contact-map visualisation, and assessments of completeness, consensus quality and phasing through K-mer analysis. It produces a comprehensive HTML report with method descriptions, tables, and visualisations. Availability and Implementation The pipeline uses NextFlow for workflow orchestration and adheres to the best-practice established by the nf-core community. This pipeline offers a reproducible, scalable, and portable method to assess the quality of genome assemblies – the code is available online.GitHub: https://github.com/Plant-Food-Research-Open/assemblyqc Supplementary information Pipeline usage documentation, parameter descriptions and example outputs are available on GitHub: https://github.com/Plant-Food-Research-Open/assemblyqc/tree/main/docs. A preview report is also hosted online: https://plant-food-research-open.github.io/assemblyqc

Milk production from Asiatic swamp buffalo is a new enterprise in Laos. As yields are limited, provision of high-quality Cow-Calf molasses nutrient blocks containing 10% urea (UMNB10) may improve productivity. A trial in a recently established commercial buffalo dairy examined dietary supplementation of lactating buffalo cows with UMNB10, with 3 groups of 9 cows in mid-lactation randomly selected. Two groups received ad-libitum access to UMBs with the remaining group free of block supplements. All animals were daily fed fresh Napier grass (30kg), corn (750gm), rice bran (1.45kg), plus accessed fresh Mulatto grass. Daily milk production (DMP) and body condition score (BCS) were recorded for the 2 months of access to UMB. Average DMP for the 2 supplemented groups were 1.02 litres and 0.96 litres, compared to 0.78 litres for the control group, suggesting improved milk productivity of 31% and 24% from accessing UMB. Partial budget analysis identified a strong incentive for use of the molasses blocks, with a net profit of USD408 and USD295 over a 30-day period for the supplemented groups. Molasses nutrient blocks may be a simple motivator for smallholder farmers in developing countries to increase the efficiency of large ruminant production, improving rural livelihoods, food security and potentially, reducing GHG emissions.

In contrast to Th1 immune responses against pathogenic viruses and bacteria, the incipient events that generate Th2 responses remain less understood. Part of the difficulty in identifying universal operating principles stems from the diversity of entities against which cellular and molecular Th2 responses are produced. Indeed, such responses are launched towards harmful macroscopic parasites and noxious substances such as venoms but also against largely innocuous allergens. This suggests that the canonical understanding about sensing and recognition applied to Th1 responses may not be translatable to Th2 responses. This review will discuss processes and signals known to occur in Th2 responses, particularly in the context of food allergy. We propose that perturbations of homeostasis at barrier sites induced by external or internal subverters that either activate the immune system or lower its threshold activation are the major requirement for allergic sensitization. Innate signals produced in the tissue under these conditions equip dendritic cells with a program that shapes an adaptive Th2 response.

Little is understood about the impact of nebulisation on the viability of SARS-CoV-2. In this study, a range of nebulisers with differing methods of aerosol generation were evaluated to determine SARS-CoV-2 viability following aerosolisation. The aerosol particle size distribution was assessed using an aerosol particle sizer (APS) and SARS-CoV-2 viability was determined after collection into liquid media using All-Glass Impingers (AGI). Viable particles of SARS-CoV-2 were further characterised using the Collison 6-jet nebuliser in conjunction with novel sample techniques in an Andersen size-fractioning sampler to predict lung deposition profiles. Results demonstrate that all the tested nebulisers can generate stable, polydisperse aerosols (Geometric standard deviation (GSD) circa 1.8) in the respirable range (1.2 to 2.2µm). Viable fractions (PFU/particle, the virus viability as a function of total particles produced) were circa 5x10^-3 and were not significantly affected by relative humidity. The novel Andersen sample collection methods successfully captured viable virus particles across all sizes; with most particle sizes below 3.3µm. MMADs (Mass Median Aerodynamic Diameters) were calculated from linear regression of log10-log10 transformed cumulative PFU data, and calculated MMADs accorded well with APS measurements and did not differ across collection method types. This data will be vital in informing animal aerosol challenge models, and infection prevention and control policies.

As a major infectious disease in chickens, Newcastle disease causes considerable economic losses in the poultry industry, especially in developing countries where there is limited access to effective vaccination. Therefore, enhancing resistance to the virus in commercial chickens through breeding is a promising way to promote poultry production. In this study, we investigated gene expression changes at 2 and 6 dpi after infection at day21 with a lentogenic Newcastle disease virus in a commercial egg-laying chicken hybrid using RNA sequencing analysis. By comparing NDV challenged and nonchallenged groups, 526 differentially expressed genes (DEGs) (FDR &lt; 0.05) were identified at 2 dpi, and only 36 at 6 dpi. For the DEGs at 2 dpi, IPA analysis predicted inhibition of multiple signaling pathways in response to NDV that regulate immune cell development and activity, neurogenesis and angiogenesis. Upregulation of Interferon Induced Protein with Tetratricopeptide Repeats 5 (IFIT5) in response to NDV was consistent between the current and most previous studies. Sprouty RTK Signaling Antagonist 1 (SPRY1), a DEG in the current study is located in a significant QTL associated with virus load at 6 dpi in the same population. These identified pathways and DEGs provide potential targets to further study breeding strategy to enhance NDV resistance in chickens.

The ongoing global pandemic caused by coronavirus disease 2019 (COVID-19) has once again demonstrated the significance of the Coronaviridae family in causing human disease outbreaks. As SARS-CoV-2 was first detected in December 2019, information on its tropism, host range, and clinical presentation in animals is limited. Given the limited information, data from other coronaviruses may be useful to inform scientific inquiry, risk assessment and decision-making. We review the endemic and emerging alpha- and betacoronavirus infections of wildlife, livestock, and companion animals, and provide information on the receptor usage, known hosts, and clinical signs associated with each host for 15 coronaviruses discovered in people and animals. This information can be used to guide implementation of a One Health approach that involves human health, animal health, environmental, and other relevant partners in developing strategies for preparedness, response, and control to current and future coronavirus disease threats.

Online reinforcement learning (RL) algorithms are increasingly used to personalize digital interventions in the fields of mobile health and online education. Common challenges in designing and testing an RL algorithm in these settings include ensuring the RL algorithm can learn and run stably under real-time constraints, and accounting for the complexity of the environment, e.g., a lack of accurate mechanistic models for the user dynamics. To guide how one can tackle these challenges, we extend the PCS (Predictability, Computability, Stability) framework, a data science framework that incorporates best practices from machine learning and statistics in supervised learning (Yu and Kumbier, 2020), to the design of RL algorithms for the digital interventions setting. Further, we provide guidelines on how to design simulation environments, a crucial tool for evaluating RL candidate algorithms using the PCS framework. We illustrate the use of the PCS framework for designing an RL algorithm for Oralytics, a mobile health study aiming to improve users' tooth-brushing behaviors through the personalized delivery of intervention messages. Oralytics will go into the field in late 2022.

Background and Objectives: Overuse and inappropriate use of testing and hospital admission are common in syncope evaluation and management. Though guidelines are available to optimize syncope care, study suggested that the current clinical guidelines have not significantly impacted resource utilization surrounding emergency department (ED) evaluation of syncope. Matching implementation strategies to barriers and facilitators and tailoring strategies to local context hold significant promise for a successful implementation of clinical practice guideline (CPG). Our team applied implementation science principles to develop a stakeholder-based implementation strategy. Methods and Materials: We partnered with patients, family caregivers, frontline clinicians and staff, and health system administrators at four health systems to conduct quantitative surveys and qualitative interviews for context assessment. The identification of implementation strategies was done by applying the CFIR-ERIC Implementation Strategy Matching Tool and soliciting stakeholders’ inputs. We then co-designed with patients and frontline teams, developed and tested specific strategies. Results: 114 clinicians completed surveys and 32 clinicians and stake-holders participated in interviews. Results from the surveys and interview indicated low awareness of syncope guidelines, and communication challenges with patients, lack of CPG protocol integration into ED workflows, and organizational process to change were recognized as major barriers. Thirty-one patients and their family caregivers participated in interviews and ex-pressed their expectations: clarity regarding their diagnosis, context surrounding care plan and diagnostic testing, and a desire to feel cared about. After identifying change methods to address those barriers, the multilevel, multicomponent implementation strategy, MISSION, included pa-tient educational materials, mentored implementation, academic detailing, Syncope Optimal Care Pathway and corresponding Mobile App, and Lean quality improvement methods. The pilot of MISSION demonstrated feasibility, acceptability and initial success on appropriate testing. Con-clusions: Effect multifaceted implementation strategies that target individuals, teams, and healthcare systems can be employed to plan successful implementation and promote adherence to syncope CPGs.

Keywords: gender equality policy; initial teacher education; teacher educators’ perceptions; gender perspective; university teaching; sustainable development; SDG5; SDG4.

The global population is at risk of vitamin D deficiency due to low exposure to sunlight and low intake of the vitamin through diet. The aim was to investigate in women the association between vitamin D status and parathyroid hormone (PTH), ultraviolet radiation, lifestyle, ethnicity, social conditions, and residential greenness. A 1-year longitudinal study assessed vitamin D status in 309 women, latitude 51° 14' N. Blood samples were taken four times throughout the year for analysis of 25(OH)D and serum PTH concentration. After each seasonal visit, the individuals completed 4-day diet diaries and used two dosimeter badges for 1 week to estimate weekly UVR exposure. A questionnaire was applied to provide information about lifestyle and their ethnicity. Residential greenness was measured by Normalized Difference Vegetation Index (NDVI), within a 1000 m radius around each participant’s home address. Women living in greener spaces were more likely to have improved vitamin D status (RR: 1.51; 95%CI: 1.13 – 2.02), as well as those who were more exposed to UVR (RR: 2.05; 95%CI: 1.44 – 2.92). Our results provided a first insight into the connection between vitamin D, residential greenness, and lifestyle in a region of temperate climate and with a high degree of urbanization.

Immunosenescence refers to age-related alterations of the immune system function affecting both the humoral and cellular arm of immunity. Understanding immunosenescence and its impact on vaccination of older adults is essential since primary vaccine responses in older individuals can fail to generate complete protection, especially vaccines targeting infections with increased incidence among the elderly, such as the respiratory syncytial virus. Here, we review the clinical trials of both candidate and approved vaccines against respiratory syncytial virus (RSV), which include adults aged ≥50 years, with an emphasis on the evaluation of immunogenicity parameters. Currently, there are 10 vaccine candidates and 2 vaccines approved for the prevention of RSV in the older adult population. The number of registered clinical trials for this age group amounts to 32. Our preliminary evaluation of published results and interim analyses of the RSV vaccine clinical trials indicates efficacy in older adult participants, demonstrating immunity levels that closely resemble those of younger adult participants.

The Xpert® Xpress SARS-CoV-2 and Xpert® Xpress SARS-CoV-2/Flu/RSV tests were rapidly developed and widely used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In response to emerging genetic variability, a new SARS-CoV-2 target (RNA-dependent RNA-polymerase) has been added to both tests: Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus test. A rapid evaluation of both tests was performed in South Africa, using residual respiratory specimens. Residual respiratory specimens (n=125) were used to evaluate the Xpert® Xpress CoV-2 plus test and included 50 genotyped specimens. The Xpert® Xpress CoV-2/Flu/RSV plus test was assessed using 45 genotyped SARS-CoV-2 specimens, ten influenza A, ten Influenza B and twenty respiratory syncytial virus specimens. Results were com-pared to in-country standard of care tests. Genotyped specimens tested the performance of the test under pressure from circulating SARS-CoV-2 variants of concern. Reference material was included to assess the test limits and linearity. The Xpert® Xpress CoV-2 plus test performance compared to reference results across residual respiratory specimens was good (positive per-centage agreement (PPA)=95.2%, negative percentage agreement (NPA)=95.0%) The Xpert® Xpress CoV-2/Flu/RSV plus test showed good performance across all residual respiratory specimens (PPA=100%, NPA=98.3%). All genotyped variants of concern were detected by both tests. The Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus tests can be used to diagnose SARS-CoV-2, and to diagnose and differentiate SARS-CoV-2, influenza A, influenza B and respiratory syncytial virus respectively. The NPA was lower than the recommended 99%, but was influenced by the low number of negative specimens tested. The variants of concern assessed did not affect test performance. It is recommended that sites perform their own assessments compared to in-country standard of care tests.

Abstract. Babies born to severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) infected mothers are at greater risk for perinatal morbidity and more likely to receive a neurodevelopmental diagnosis in the first year of life. However, the effect of maternal infection on placental function and neonatal outcomes varies depending upon the patient population. We set out to test our hypothesis that maternal SARS-CoV-2 infection in our underserved, socioeconomically disadvantaged, predominantly African American and Latina population in the Bronx, NY would have effects evident at birth. Fifty-five SARS-CoV-2 positive and 61 negative third trimester patients were randomly selected from Montefiore Medical Center (MMC), Bronx, NY. In addition, two positive cases from Yale New Haven Hospital, CT were included as controls. All 55 placentas delivered by SARS-CoV-2 positive mothers were uninfected by the virus, based on immunohistochemistry, in-situ hybridization, and qPCR analysis. However, placental villous infarcts, mild preeclampsia, shortened gestational periods and lower Apgar scores were observed in the infected cases. These findings suggest that even without entering the placenta, SARS-CoV-2 can affect various systemic pathways culminating in altered placental development and function, which may adversely affect the fetus, especially in a high-risk patient population such as ours. These results underline the importance of vaccination among pregnant women, particularly in low resource areas.

The blackening of cut carrots decreases their shelf life and causes severe economic losses but the molecular and metabolic mechanisms that underpin this phenomenon remain poorly characterized. Studies were therefore undertaken to determine the molecular and metabolic causes of the blackening. The susceptibility of blackening was dependent on the period of time that the crop was stored underground prior to harvest. The structure of the cell walls in the black regions was substantially changed compared to the orange regions. The black regions of carrot batons had decreased immunodetection of xyloglucan, HG-pectin, RG-I pectin, galactan and arabinan but had higher levels of lignin and phenolic compounds compared to the orange regions. Transcript profiling analysis revealed that phytohormone signalling processes were activated in the black regions. Transcripts associated with auxin signalling and ethylene-responsive transcription factors were increased in the black regions. In contrast, the levels of transcripts encoding proteins associated with secondary metabolism were decreased in the black regions. These findings implicate ethylene and auxin-related processes in the control of the primary to secondary metabolism shift that results in lignification and cell wall disruption that underpin the blackening process.

Inflammation is considered an important target for stroke therapy because it induces secondary brain damage after the initial ischemic insult. Peripheral monocytes migrate to the brain parenchyma after a central insult. They then differentiate to macrophages in a positive feedback fashion contributing to damage instead of ischemic resolution and inflammation control. A cyclic diterpenoid, (1S,2E,4R,6R,7E,11E)-cembra-2,7,11-triene-4,6-diol (4R), decreases neurodegeneration after ischemia with central anti-inflammatory activity. This study aims to determine whether the central anti-inflammatory effect of 4R is effective against peripheral inflammation triggered by brain ischemia. To investigate the anti-inflammatory effect of 4R, we treated macrophages with lipopolysaccharide (LPS) as an inflammatory model, followed by treatment with 4R. Microarray transcriptome analysis of over 30,000 genes identified the differential expression of 393 genes. Genes related to inflammation, cell adhesion, and transcription were validated with qPCR, and reduced expression was determined. Quantification of NF-kB phosphorylation served as a marker for the modulation of inflammation through gene transcription. Our results show that 4R was associated with a reduction in NFKB1 and ITGB5 gene expression, increased phosphorylation of NF-kB, and a decrease in macrophage adhesion in a blood-brain barrier model. These results indicate that 4R can partially modulate the peripheral immune response, making 4R a potential drug against post-ischemic inflammation.

Glucocorticoids promote muscle atrophy by inducing a class of proteins called atrogenes, resulting in reductions in muscle size and strength. In this work, we evaluated whether a mouse model with pre-existing diet-induced obesity had altered glucocorticoid responsiveness. We observed that all animals treated with the synthetic glucocorticoid dexamethasone had reduced strength, but that obesity exacerbated this effect. These changes were concordant with more pronounced reductions in muscle size, particularly in Type II muscle fibers, and potentiated induction of atrogene expression in the obese mice relative to lean mice. Furthermore, we show that the reductions in lean mass do not fully account for the dexamethasone-induced insulin resistance observed in these mice. Together these data suggest that obesity potentiates glucocorticoid-induced muscle atrophy.

Age is the primary risk factor for neurodegenerative diseases such as Alzheimer’s and Huntington’s disease. Alzheimer’s disease is the most common form of dementia and a leading cause of death in the elderly population of the United States. No effective treatments for these diseases currently exist. Identifying effective treatments for Alzheimer’s, Huntington’s, and other neurodegenerative diseases is a major current focus of national scientific resources, and there is a critical need for novel therapeutic strategies. Here we investigate the potential for targeting the kynurenine pathway metabolite 3-hydroxyanthranilic acid (3HAA) using Caenorhabditis elegans expressing amyloid-beta or a polyglutamine peptide in body wall muscle, modeling proteotoxicity in Alzheimer’s and Huntington’s disease-related, respectively. We show that knocking down the enzyme that degrades 3HAA, 3HAA dioxygenase (HAAO) delays age-associated paralysis in both models. This effect on paralysis was independent of protein aggregation in the polyglutamine model. We also show that the mechanism of protection against proteotoxicity from HAAO knockdown is mimicked by 3HAA supplementation, supporting elevated 3HAA as the mediating event liking HAAO knockdown to delayed paralysis. This work demonstrates potential for 3HAA as a targeted therapeutic in neurodegenerative disease, though the mechanism is yet to be explored.

Proprotein convertases activate various envelope glycoproteins and participate in cellular entry of many viruses. We recently showed that the convertase furin is critical for the infectivity of SARS-CoV-2. This study investigated the implication of the two cholesterol-regulating convertases SKI-1 and PCSK9 in SARS-CoV-2 entry. We used cell-to-cell fusion assays in HeLa cells and pseudoparticle entry into Calu-3 cells. SKI-1 increases cell-to-cell fusion by enhancing the activation of SREBP-2, whereas PCSK9 reduces cell-to-cell fusion by promoting the cellular degradation of ACE2. Metalloprotease activation is sensitive to enhanced cholesterol levels resulting from SKI-1-activated SREBP-2 that leads to enhanced S2’ formation. However, high metalloprotease activity results in S2’ shedding into a new C-terminal fragment (S2”), leading to reduced cell-to-cell fusion. Indeed, S-mutants that increase S2’’ formation, abolish S2’ and cell-to-cell fusion, as well as pseudoparticles entry, indicating that the formation of S2’’ prevents SARS-CoV-2 cell-to-cell fusion and entry. We next demonstrated that PCSK9 enhanced the cellular degradation of ACE2, thereby reducing cell-to-cell fusion. However, different from the LDLR, a canonical target of PCSK9, the C-terminal CHRD domain of PCSK9 is dispensable for the PCSK9-induced degradation of ACE2. Molecular modeling suggested binding of ACE2 to the Pro/Catalytic domains of mature PCSK9. Thus, both cholesterol-regulating convertases SKI-1 and PCSK9 can modulate SARS-CoV-2 entry via two independent mechanisms.

Colorectal cancer is a common disease, both in Chile and worldwide. The most widely used chemotherapy schemes are based on 5-fluorouracil (5FU) as the foundational drug. Genetic polymorphisms have emerged as potential predictive biomarkers of response to chemotherapy, but conclusive evidence is lacking. Additionally, the interplay between hereditary variations and acquired mutations in the EGFR pathway remains unknown. This study aimed to investigate the role of genetic variants associated with 5FU-based chemotherapy on therapeutic effectiveness, considering their interaction with the EGFR pathway mutations. In a retrospective cohort of 63 patients diagnosed with metastatic colorectal cancer, a multivariate analysis revealed that liver metastases, DPYD, ABCB1 and MTHFR polymorphisms are independent indicators of a poor prognostic, irrespective of EGFR pathway mutations. BRAF V600E wild-type status and high-risk drug-metabolism polymorphisms correlated with a poor prognosis in this Chilean cohort. Additionally, findings from the genomics of drug sensitivity (GDSC) project demonstrated that cell lines with wild-type BRAF have higher IC50 values for 5-FU compared to BRAF-mutated cell lines. In conclusion, the genetic polymorphisms DPYD rs1801265, ABCB1 rs1045642 and MTHFR rs180113 may serve as useful biomarkers for predicting a poor prognosis in patients undergoing 5-fluorouracil chemotherapy, regardless of EGFR pathway mutations.

Leukemia, contributing to 3% of all cancer cases in the United States, presents a significant challenge in treatment due to its diverse subtypes, each dis-playing unique genetic and molecular abnormalities. The aggressive growth of ab-normal blood cells compromises immune function and poses challenges in developing effective therapeutic approaches. Unlike solid tumors, surgical resection is not an option, limiting treatment strategies to chemotherapy, immunotherapy, and radiation therapy, which may be nonspecific and lead to organ damage and toxicity. Anthracyclines, widely used in hematological tumors, face limitations due to severe cardiotoxicity, causing progressive cardiomyopathy and, in severe cases, congestive heart failure. Heart failure incidence is significantly higher in cancer patients treated with anthracyclines over 5, 10, and 15 years. Early detection of left ventricular dysfunction and cardiotoxicity is crucial to mitigate progression to congestive heart failure (CHF) in this population. Recent research by Bayrón-Marrero et al. reveals that lower levels of plasma soluble TREM-Like Transcript-1 (s-TLT-1), a platelet-specific receptor, correlate with left ven-tricular dysfunction in cardiovascular disease patients. Those with s-TLT-1 levels ex-ceeding 544 pg/mL exhibit a significant association with congestive heart failure. These findings suggest the potential use of s-TLT-1 as a diagnostic screening tool for early detection and treatment of anthracycline-induced CHF in leukemia patients.

Windthrow (i.e., trees broken and uprooted by wind) is a major natural disturbance in the Amazon. Images from medium-resolution optical satellites (mostly Landsat) combined with extensive field data have allowed researchers to assess patterns of tree mortality and monitor forest recovery over decades of subsequent succession in different regions. Although satellites with high spatial-resolution have become available for the Amazon in the last decade, they have not yet been employed for the mapping and quantification of windthrow tree-mortality. Here, we address how increasing the spatial resolution of satellites affects plot-to-landscape estimates of windthrow tree-mortality. We combined forest inventory data with Landsat 8 (30 m pixel), Sentinel 2 (10 m), and WorldView 2 (2 m) imagery over an old-growth forest in the Central Amazon that was disturbed by a single windthrow event in November/2015. Remote sensing estimates of tree mortality were produced with Spectral Mixture Analysis and analyzed together with forest inventory data using Generalized Linear Models. Windthrow tree-mortality measured in 3 transects (30 subplots) crossing the entire disturbance gradient was 26.9 ± 11.1% (mean ± 95% CI). Based on this ground truth, the three satellites produced reliable and statistically similar estimates (from 26.5% to 30.3% windthrow tree-mortality, p&lt;0.001). The mean-associated uncertainties decreased systematically with increasing spatial resolution (i.e., from Landsat 8 to Sentinel 2 and WorldView 2). However, the overall quality of fit of models showed the opposite pattern, which may reflect the influence of crown damage not accounted for in our field study, and fast-growing regeneration of leaf area. Among the satellites studied, Landsat 8 most accurately captured field observations of variations in tree mortality across the disturbance gradient (i.e., lower under- and/or overestimation from undisturbed to extremely damaged forest). Although satellites with high spatial-resolution can refine estimates of windthrow severity by allowing the quantification of individual tree damage and mortality, our results validate the reliability of Landsat imagery for assessing patterns of windthrow tree-mortality in dense and heterogeneous tropical forests. Although high-resolution imagery may improve estimates of tree damage and mortality, these should be validated using field data at compatible scales.

Heat stress results in significant economic losses to the poultry industry. Genetics plays an important role in chickens adapting to the warming environment. Physiological parameters, including hematochemical parameters, change in response to heat stress in chickens. To explore the genetics of heat stress resilience in chickens, a genome-wide association study (GWAS) was conducted using Hy-Line Brown (HLB) layer chicks treated with either high ambient temperature or combined high temperature and Newcastle disease virus (NDV) infection. Hematochemical parameters were measured during three treatment phases: acute heat stress, chronic heat stress, and chronic heat stress combined with NDV infection. Significant changes in blood parameters were recorded for 11 parameters across the three treatments. The GWAS revealed 39 significant SNPs (P < 0.05) for 7 parameters, located on Gallus gallus chromosomes (GGA) 1, 3, 4, 6, 11, and 12. The significant genomic regions were further investigated to examine if the genes within the regions were associated with the corresponding traits under heat stress. A candidate gene list including genes in the identified genomic regions that were also differentially expressed in chicken tissues under heat stress was generated. Understanding the correlation between genetic variants and resilience to heat stress is an important step in improving heat tolerance in poultry.

Human pluripotent stem cells (hPSCs) have widespread potential biomedical applications. There is a need for large-scale in vitro production of hPSCs, and optimal culture methods are vital in achieving this. Physiological oxygen (2% O2) improves key hPSCs attributes, including genomic integrity, viability, and clonogenicity, however, its impact on hPSC metabolism remains un-clear. Here, Selected Ion Flow Tube-Mass Spectrometry (SIFT-MS) was used to detect and quantify metabolic Volatile Organic Compounds (VOCs) in the headspace of hPSCs and their differentiated progeny. hPSCs were cultured in either 2% O2 or 21% O2. Media was collected from cell cultures and transferred into glass bottles for SIFT-MS measurement. The VOCs acetaldehyde and dimethyl sulfide (DMS)/ethanethiol were significantly increased in undifferentiated hPSCs compared to their differentiating counterparts, and these observations were more apparent in 2% O2. Pluripotent marker expression was consistent across both O2 concentrations tested. Transcript levels of ADH4, ADH5, and CYP2E1, encoding enzymes involved in converting ethanol to acetaldehyde, were upregulated in 2% O2, and chemical inhibition of ADH and CYP2E1 decreased acetaldehyde levels in hPSCs. Acetaldehyde and DMS/ethanethiol may be indicators of altered metabolism pathways in physiological oxygen culture conditions. The identification of non-destructive biomarkers for hPSC characterization has the potential to facilitate large-scale in vitro manufacture for future biomedical application.

Lentiviral vectors (LVs) are a powerful tool for gene and cell therapy and human embryonic kidney cells (HEK293) have been extensively used as a platform for production of these vectors. Like most cells and cellular tissues, HEK293 cells release extracellular vesicles (EVs). EVs released by cells share similar size, biophysical characteristics and even a biogenesis pathway with cell-produced enveloped viruses, making it a challenge to efficiently separate EVs from LVs. Thus, EVs co-purify with LVs during downstream processing, becoming “impurities” in the context of cell therapy. To characterize EVs from an inducible lentivirus producing cell line, two conditions were studied: non-induced and induced. EVs’ identity was confirmed by transmission electron microscopy and western blot. Seven proteins were identified by mass spectrometry as potential EV markers. Lipid composition of EVs and LVs showed similar enrichment in phosphatidylserine. RNA cargos in EVs showed enrichment in genes involved in viral processes and binding functions. Flow virometry, GTA and ddPCR results also confirmed the heterogenic nature of EVs and LVs populations. These findings provide insights on the product profile of lentiviral preparation and could help develop separation strategies of co-produced EVs.

Background: Colorectal cancer (CRC) patients experienced multiple chemotoxicity affecting treatment compliance, survival, and quality of life (QOL). Prior research shows clinician-reported chemotoxicity (i.e., grading scales or diagnostic codes) predicts rehospitalization and cancer survival. However, a comprehensive synthesis of clinician-reported chemotoxicity is still lacking. Objectives: We conducted a systematic review and meta-analysis to determine the chemotoxicity's prevalence and risk factors in CRC. Methods: A systematic search from 2009 to 2024 yielded 30 studies for review, with 25 included in the meta-analysis. Results: Pooled prevalences of overall, non-hematological, and hematological moderate-to-severe toxicities were 45.7%, 39.2%, and 25.3%, respectively. The most common clinician-reported chemotoxicities were gastrointestinal (GI) toxicity (22.9%) and neuropathy or neutropenia (17.9%). Significant risk factors at baseline were malnutritional status, frailty, impaired immune or hepato-renal functions, short telomere lengths, low gut lactobacillus levels, age, female sex, aggressive chemotherapy, and low QOL. Age was associated with neutropenia (β: -1.44) and GI toxicity (β:1.85) (Ps 65 y.o.) had higher prevalences of overall (OR: 1.14) and GI (OR: 1.65) toxicities, but a lower prevalence of neutropenia (OR: 0.65) than younger adults (Ps

Bioenergy with carbon capture and sequestration (BECCS) is one strategy to remove CO2 from the atmosphere. To assess the potential scale and cost of CO2 sequestration from BECCS in the US, this analysis models carbon efficiencies and costs of biomass production, delivery, power generation, and CO2 capture and sequestration in saline formations. The analysis includes two biomass supply scenarios (near-term and long-term), two biomass logistics scenarios (conventional and pelletized), two generation technologies (pulverized combustion and integrated gasification combined cycle), and three cost accounting scenarios (gross cost, net cost after electricity revenues, and net cost after electricity revenues with avoided emissions from conventional power generation). Results show cost Mg-1 CO2 as a function of CO2 sequestered (simulating capture up to 90% of total CO2 sequestration potential) and associated spatial distribution of resources and generation locations for the array of scenario options. Under a near-term scenario using 222 million Mg yr-1 of biomass, up to 196 million Mg CO2 can be sequestered at scenario-average costs ranging from $60 to $158 Mg 1 CO2; under a long-term scenario using 823 million Mg yr-1 of biomass, up to 727 million Mg CO2 yr 1 can be sequestered at scenario-average costs ranging from $32 to $242 Mg-1 CO2. These costs are largely influenced by cost accounting scenario, and the CO2 sequestration potential may be reduced if future competing demand reduces resource availability. Results suggest there are multiple feedstock-logistics-generation pathways toward CO2 drawdown that could be incrementally trialed and monitored for environmental sustainability effects. Interactive visualization of results is available at [final link to be determined].

In the face of rising global demand and unsustainable production methods, cultivated crustacean meat (CCM) is proposed as an alternative means to produce delicious lobster, shrimp and crab products. Cultivated meat requires starting stem cells that may vary in terms of potency, and propensity to proliferate or differentiate into myogenic (muscle-related) tissues. We suggest that regenerating crustacean limbs harbor a range of stem cells suitable for cultivated meat production and present a humane tissue source because they can be accessed non-lethally. To investigate stem cell activity in this model, we have conducted RNA-Seq analysis across six stages of claw regeneration in the crayfish Cherax quadricarinatus (four pre-molt and two post-molt stages), along with histology and real time quantitative PCR (qPCR). Differential expression analysis revealed expression patterns of significantly up- or down-regulated genes in 14 functional categories. Relative expression of select stem cell target genes (including endocrine, myogenic, cell cycle and pluripotency factors) highlighted two growth peaks during pre-molt regeneration and limited stem cell activity after the molt. Histology and qPCR results support the overall finding that pre-molt limb regeneration stages harbor more stem cell activity, likely making them a more prolific cell source for CCM development.

This study investigated co-constructed research poetry as a way to understand the lived experiences of people affected by rarer dementia and as a means to use poetry to convey those experiences to healthcare professionals. Using mixed-methods, 71 people living with rarer dementia and care-partners (stakeholders) contributed to co-constructing 27 poems with professional poets; stakeholders’ verbatim words were analysed with descriptive qualitative analysis. Stakeholders were also surveyed and interviewed about their participation. Healthcare professionals (n = 93) were surveyed to elicit their responses to learning through poetry and its acceptability as a learning tool. Poems conveyed a shared narrative of different aspects of lived experience, often owing to atypical symptoms, misunderstandings by professionals, lack of support pathways, and a continuous struggle to adapt. Stakeholder surveys indicated it was a valuable experience to both co-create and respond to the poems, whilst group interviews revealed people’s experiences of the research poetry were characterised by reflection on lived experience, curiosity and exploration. Healthcare professionals’ responses reinforced the poetry’s capacity to stimulate cognitive and affective learning specific to rare dementia support and prompt both empathy and critical thinking in practice. As the largest poetry-based study that we are aware of, this novel accessible approach of creating group poems yielded substantial information about the experiences and needs of those affected by rarer dementia and how poetry can contribute to healthcare education and training.

Global climate change requires urgent solutions. Ambitious tree-planting initiatives, many already underway, aim to sequester enormous quantities of carbon, partly compensating for the anthropogenic CO₂ emissions that are a major cause of rising global temperatures. However, poorly planned and executed tree-planting could actually increase CO₂ emissions and have long-term, deleterious impacts on biodiversity, landscapes and livelihoods. Here, we highlight the main environmental risks of large-scale tree planting and propose ten golden rules, based on some of the most recent ecological research, to implement forest ecosystem restoration that maximizes rates of both carbon sequestration and biodiversity recovery, while simultaneously improving livelihoods. These are: i) Protect existing forest first; ii) Work together (involving all stakeholders); iii) Maximize biodiversity recovery to meet multiple goals; iv) Select appropriate areas; v) Use natural regeneration wherever possible; vi) Select species to maximise biodiversity; vii) Use resilient plant material (with appropriate genetic variability and provenance); viii) Plan ahead for infrastructure, capacity and seed supply; ix) Learn by doing (using an adaptive management approach); and x) Make it pay (ensuring the economic sustainability of the project). We focus on the design of long-term strategies to tackle the climate and biodiversity crises and support livelihood needs. We emphasize the role of local communities and their dependence on benefits from successful reforestation programmes that restore ecosystem functioning and deliver a diverse range of forest products and services. While there is no simple and universal recipe for forest restoration, it is now crucial to build on the public and private interest in this topic to ensure interventions provide effective, long-term carbon sinks and maximise benefits for biodiversity and people.

The high demand for SARS-CoV-2 tests but limited supply to South African laboratories early in the COVID19 pandemic, resulted in a heterogenous diagnostic footprint of open and closed molecular testing platforms. Novel approaches were required to monitor test quality especially during the introduction of newly circulating variants. The National Health Laboratory Service centrally collected cycle threshold (Ct) values from 1,497,669 test results reported from six commonly used PCR assays in 36 months, and visually monitored changes in their median Ct within a 28-day centered moving average for each assays’ gene targets. This continuous quality monitoring rapidly identified delayed hybridization of RdRp in the Allplex™ SARS-CoV-2 assay due to the Delta (B.1.617.2) variant; S-gene target failure in the TaqPath™ COVID-19 assay due to B.1.1.7 (Alpha) and the B.1.1.529 (Omicron); and recently E-gene delayed hybridization in the Xpert® Xpress SARS-CoV-2 due to XBB.1.5. This near “real-time” monitoring helped inform the need for sequencing and the importance of multiplex molecular nucleic acid amplification technology designs used in diagnostics for patient care. This continuous quality monitoring approach at the granularity of Ct values should be included in ongoing surveillance and with application to other disease use cases that rely on molecular diagnostics.

Gene editing tools such as CRISPR-Cas9 have created unprecedented opportunities for genetic studies in plants and animals. We designed a course-based undergraduate research experience (CURE) to train introductory biology students in the concepts and implementation of gene editing technology as well as develop their soft skills in data management and scientific communication. We present two versions of the course that can be implemented with twice-weekly meetings over a five-week period. In the remote-learning version, students perform homology searches, design guide RNAs and primers, and learn the principles of molecular cloning. This version is appropriate when access to laboratory equipment or in-person instruction is limited, such as closures that have occurred in response to the Covid-19 pandemic. In the in-person version, students design guide RNAs, clone CRISPR-Cas9 constructs, and perform genetic transformation of the model plant Arabidopsis thaliana. The highly parallel nature of the CURE makes it possible to target dozens to hundreds of genes, depending on the number of course sections available. Applying this approach in a sensitized mutant background enables focused reverse genetic screens for genetic suppressors or enhancers. The course can be readily adapted to other organisms or projects that employ gene editing.

Herpes simplex virus (HSV) infections can be treated with direct acting antivirals like acyclovir and foscarnet, but long-term use can lead to drug resistance, which motivates research into broadly-acting antivirals that can provide a greater genetic barrier to resistance. Photodynamic inactivation (PDI) employs a photosensitizer, light, and oxygen to create a local burst of reactive oxygen species that inactivate microorganisms. The botanical plant extract Orthoquin^TM is a powerful photosensitizer with antimicrobial properties. Here we report that Orthoquin also has antiviral properties. Photoactivated Orthoquin inhibited herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) infection of target cells in a dose-dependent manner, across a broad range of sub-cytotoxic concentrations. HSV inactivation required direct contact between Orthoquin and the inoculum, whereas pre-treatment of target cells had no effect. Orthoquin did not cause appreciable damage to viral capsids or pre-mature release of viral genomes as measured by qPCR for the HSV-1 genome. By contrast, immunoblotting for HSV-1 antigens in purified virion preparations suggested that higher doses of Orthoquin had a physical impact on certain HSV-1 proteins that altered protein mobility or antigen detection. Orthoquin PDI also inhibited the non-enveloped adenovirus (AdV) in a dose-dependent manner, whereas Orthoquin-mediated inhibition of the enveloped vesicular stomatitis virus (VSV) was light-independent. Together, these findings suggest that broad antiviral effects of Orthoquin-mediated PDI may stem from damage to viral attachment proteins.

Older adults with obesity have an increased risk for cognitive decline and subsequent Alzheimer’s disease. Previous research has focused on the impact of individual nutrients and overall dietary patterns to improve cognitive function. The Brain and Body Health (BB-Health) study aims to demonstrate the feasibility of a multicomponent nutritional supplement (MCNS) and weight loss (WL) intervention for individuals with overweight and obesity who are not consuming a healthy diet. BB-Health is a parallel-group randomized placebo-controlled 2x2 factorial pilot trial comparing the MCNS, WL, and MCNS+WL with a Control group. Eligible participants are 55 to 85 years of age with a body mass index 27.0 to 39.9 kg/m2. Major exclusion criteria include type 2 diabetes, moderate or severe cognitive impairment, and self-reported healthy dietary pattern. The BB-Health feasibility trial is registered as NCT05542199 at clinicaltrials.gov. The BB-Health objectives are to report: 1) recruitment and enrollment, including pace and descriptive statistics of the study sample; 2) adherence to the administered interventions; 3) successful data collection and performance of outcome assessments, including evaluation of change in key outcomes over time that are powered for this pilot study; and 4) summary statistics on outcomes for use in planning a subsequent, larger trial. The outcomes of interest are age-sensitive cognitive assessments, cerebral hemodynamics, and related health parameters. All measurements are collected at baseline, 3-, 6-, and 12-month visits. If the BB-Health protocol demonstrates feasibility, the novel MCNS with and without a parallel WL intervention has potential to be administered in a confirmatory randomized trial to evaluate ability to prevent age-related cognitive decline and improve brain health. The BB-Health Feasibility Study could significantly contribute to our understanding of the influence of diet and weight management on cognitive health

The 2020-2025 Dietary Guidelines for Americans recommends limiting intakes of saturated fat and added sugars (SF/AS) to 88% of the representative sample of U.S. adults. The top sources of SF were cheese, pizza, ice cream, and eggs. The leading sources of AS were soft drinks, tea, fruit drinks, and cakes and pies. This analysis reflects a parsimonious approach to reliably identify foods and beverages that contribute to SF/AS intakes in U.S. adults.

leaf beetle (BLB) (Ootheca mutabilis) has emerged as an important bean pest in Uganda, leading to devastating crop losses. There is limited information on the population genetic structure of BLB despite their importance. In this study, novel microsatellite markers and the partial mitochondrial cytochrome oxidase subunit I (mtCOI) gene sequences were used to analyze the spatial population genetic structure, genetic differentiation, gene flow and haplotype diversity of 87 O. mutabilis samples from five populations. We identified 19,356 simple sequence repeats (SSRs) (mono, di, tri, tetra, penta, and hexa-nucleotides) of which 81 di, tri and tetra-nucleotides were selected for primer synthesis. Five highly polymorphic SSR markers (4-21 alleles, heterozygosi-ty 0.59-0.84, polymorphic information content (PIC) 50.13-83.14%) were used for this study. Analyses of the five O. mutabilis populations with these five novel SSRs found 89% of genetic variation occurring within individuals, 9% among individuals and 2% among populations. Genetic differentiation was low but significant for SSR and insignificant for mtCOI partial sequence data while gene flow was high across the populations. There was no evidence of isolation by distance between geographical and genetic distances. Bayesian clustering identified signature of admixture that suggests genetic contributions from two ancestral genetic lineages, and the median-joining haplotype network showed low differentiation of many different haplotypes from the most common haplotype. Low genetic differentiation and high gene flow indicates unrestricted migrations between populations. This information will contribute to the design of BLB control strategies.

SARS-CoV-2 infects a range of host species. However, the susceptibility of companion animals to SARS-CoV-2 and their potential ability to transmit the virus to humans remains unclear. Here, we present a detailed clinical description of an immunosuppressed dog that was infected with SARS-CoV-2. The dog had severe gastrointestinal (GI) clinical signs, coagulopathy, elevated hepatic transaminases, and met canine systemic inflammatory response syndrome criteria, without respiratory clinical signs, mirroring a subset of humans with GI-restricted COVID-19. Viral sequencing demonstrated divergence from other reported sequences, based on phylogenetic analysis. The dog shed high levels of virus for a prolonged time period with positive virus isolation. The dog’s immunosuppressed state may have increased both susceptibility to infection and disease progression. Together, our findings suggest that certain individual companion animals may be at higher risk for severe SARS-CoV-2 infection, COVID-19-like disease, and high viral shedding, which may pose a transmission risk to humans.

Manuka honey (MH) exhibits potential antitumor activity in preclinical models of a number of human cancers. Treatment in vitro with MH at concentrations ranging from 0.3-5.0% (w/v) led to significant dose-dependent inhibition of proliferation of human breast cancer MCF-7 cells, but anti-proliferative effects of MH were less pronounced in triple-negative MDA-MB-231 breast cancer cells. Effects of MH were also tested on non-malignant human mammary epithelial cells (HMEC) at 2.5% w/v, and it was found that MH reduced proliferation of MCF-7 cells but not that of HMEC. Notably, the antitumor activity of MH was in the range of that exerted by treatment of MCF-7 cells with the antiestrogen tamoxifen. Further, MH treatment stimulated apoptosis of MCF-7 cells in vitro, with most cells exhibiting acute and significant levels of apoptosis that correlated with PARP activation. Additionally, effects of MH induced activation of AMPK and inhibition of AKT/mTOR downstream signaling. Treatment of MCF7 cells with increased concentrations of MH induced AMPK phosphorylation in a dose dependent manner that was accompanied by inhibition of phosphorylation of AKT and mTOR downstream effector protein S6. In addition, MH reduced phosphorylated STAT3 levels in vitro which may correlate with MH and AMPK-mediated anti-inflammatory properties. Further, in vivo, MH administered alone significantly inhibited the growth of established MCF-7 tumors in nude mice by 84%, resulting in an observable reduction in tumor volume. Our findings highlight the need for further research into the use of natural compounds, such as MH, for antitumor efficacy and potential chemoprevention and investigation of molecular pathways underlying these actions.

Objective: In this work, we evaluated the chemical composition by chromatography coupled to mass spectrometry, antimicrobial and insecticidal activity of essential oils (TrEO) and nanoeffu-sion (NTrEO) of oil from Tetradenia riparia leaves. We also evaluated the acute toxicity in Mus musculus. The results showed that S. aureus showed greater susceptibility to TrEO, with a minimum inhibitory concentration (MIC) of 125 µg.mL-1, when compared to P. aeruginosa, E. coli, which presented a MIC of 250 µg.mL-1. There was a greater toxic effect on TrEO (LC50 = 630.29 µg.mL-1) and NTrEO (LC50 = 713.68 µg.mL-1) larvae, effect on pupae (LC50 = 630.29 µg.mL-1) and NTrEO (LC50 = 713.68 µg.mL-1) and ovicide (LC50 = 631.184 µg.mL-1) and NTrEO (LC50 = 146.701 µg.mL-1) of Ae. aegypti after 24 h of exposure, when compared to other exposure periods. Chemical analysis re-vealed 20 components, aromadendrene oxide (23.47%) being the main component. Female and male mice were used to assess toxicity and oral administration of NTrEO to mice did not result in acute toxicity. Thus, the essential oil of T. riparia and its nanoemulsion have insecticidal and an-timicrobial potential for Ae. aegypti, S. aureus, E. coli, P. aeruginosa, and has a high toxicological safety threshold at the concentrations evaluated in this study.

Gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) are rare cancers consisting of neuroendocrine carcinomas (NECs) and neuroendocrine tumors (NETs), which have been increasing in incidence in recent years. Few cell lines and pre-clinical models exist for the study of GEP NECs and NETs, limiting the ability to discover novel imaging and treatment modalities. To address this gap, we isolated tumor cells from cryopreserved patient GEP NECs and NETs and injected them into the flanks of immunocompromised mice to establish patient-derived xenograft (PDX) models. Two of 6 mice developed tumors (NEC913 and NEC1452). Over 90% of NEC913 and NEC1452 tumor cells stained positive for Ki67. NEC913 PDX tumors expressed neuroendocrine markers such as chromogranin A (CgA), synaptophysin (SYP), and somatostatin receptor-2 (SSTR2) whereas NEC1452 PDX tumors do not express SSTR2. Exome sequencing revealed loss of p53 and RB1 in both tumors. To demonstrate an application of these novel NEC PDX models for SSTR2-targeted peptide imaging, the NEC913 and NEC1452 cells were bilaterally injected into mice. Near infrared-labelled octreotide was administered and fluorescent signal was specifically observed for the NEC913 SSTR2 positive tumors. These 2 GEP NEC PDX models serve as valuable resource for GEP NEN therapy testing.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with heterogeneous and complex genetic underpinnings. Our previous microarray gene-expressed profiling identified significantly different neuregulin-2 (NRG2) gene expressions between ASD patients and controls. Thus, we aimed to clarify whether NRG2 is a candidate gene associated with ASD. The study consisted of two stages. First, we used real-time quantitative PCR in 20 ASDs and 20 controls to confirm the microarray gene expression profiling results. The average NRG2 gene expression level in patients with ASD (3.23±2.80) was significantly lower than that of controls (9.27±4.78, p < 0.001). Next, we resequenced all exons of NRG2 in other 349 ASD subjects, who were compared with super-controls from the Taiwan Biobank using case-control association analysis to determine the existence of mutations or single-nucleotide polymorphisms (SNPs). We identified three SNPs, including two noncoding ones, IVS3 + 13A > G (rs889022) and IVS9 + 32T > A (rs182642591), and one insertion/deletion (indel) SNP, named indel GCCCGGC, rs1323957797, in the NRG2 coding region. The genotype and allele frequency distribution of rs1323957797 significantly differed between ASDs and controls (p < 0.0001). Our findings showed significant differences in genotype and allele frequency distribution of the indel SNP, rs1323957797, located in the EGF-like domain region at the C-terminal of the NRG2 precursor protein. Together with our findings, the indel SNP mutation was significantly more common in ASDs than controls, leading to lower NRG2 expression than controls, influencing NRG2 function. Our study’s findings suggest that NRG2 is a susceptibility gene for ASD.

Recent studies have confirmed that lung microvascular endothelial injury plays a critical role in the pathophysiology of COVID-19. Our group and others have demonstrated the beneficial effects of H2S in several pathological processes and provided a rationale for considering the therapeutic implications of H2S in COVID-19 therapy. Here, we evaluated the effect of the slow-releasing H2S donor, GYY4137, on the barrier function of a lung endothelial cell monolayer in vitro, after challenging the cells with plasma samples from COVID-19 patients or inactivated SARS-CoV-2 virus. We also assessed how the cytokine/chemokine profile of patients’ plasma, endothelial barrier permeability, and disease severity correlated with each other. Alterations of barrier permeability after treatments with patient plasma, inactivated virus, and GYY4137 were monitored and assessed by electrical impedance measurements in real-time. We present evidence that GYY4137 treatment reduced endothelial barrier permeability after plasma challenge and completely reversed the endothelial barrier disruption caused by inactivated SARS-CoV-2 virus. We also showed that disease severity correlated with the cytokine/chemokine profile of the plasma but not with barrier permeability changes in our assay. Overall, these data demonstrate that treatment with H2S-releasing compounds has the potential to ameliorate SARS-CoV-2–associated lung endothelial barrier disruption.

Cancer-related fatigue is a common, burdensome symptom of cancer and side-effect of chemotherapy. While a Mediterranean Diet (MedDiet) promotes energy metabolism and overall health, its effects on cancer-related fatigue remain unknown. In a randomized controlled trial, we evaluated a rigorous MedDiet intervention for feasibility and safety as well as preliminary effects on cancer-related fatigue and metabolism compared to usual care. Participants had stage I-III cancer and at least 6 weeks of chemotherapy scheduled. After baseline assessments, randomization occurred 2:1, MedDiet:usual care. Measures were collected at baseline, week 4, and week 8 including MedDiet adherence, dietary intake, and blood-based metabolic measures. Mitochondrial respiration from freshly isolated T cells was measured at baseline and 4 weeks. Participants (n=33) were 51.0±14.6 years old, 94% were female, and 91% were being treated for breast cancer. The study was feasible, with 100% completing the study and >70% increasing their MedDiet adherence at 4 and 8 weeks compared to baseline. Overall, the MedDiet intervention vs. usual care had a small-moderate effect on change in fatigue at weeks 4 and 8. For those with a baseline MedDiet score<5 (n=21), the MedDiet intervention had a moderate-large effect of 0.67 and 0.48 at weeks 4 and 8, respectively. The MedDiet did not affect blood-based lipids, though it had a beneficial effect on fructosamine (ES= -0.55). Fatigue was associated with mitochondrial dysfunction including lower basal respiration, maximal respiration, and spare capacity (p<0.05 for FACIT-F fatigue subscale and BFI, usual fatigue). In conclusion, the MedDiet was feasible and attenuated cancer-related fatigue among patients undergoing chemotherapy, especially those with lower MedDiet scores at baseline.

Introduction: The COVID-19 pandemic overwhelmed health systems globally, and affected delivery of other health services. We conducted a study in Uganda to describe interventions for continuity of access to other health services. Methods: We reviewed documents and interviewed 21 key informants. Thematic analysis was conducted to identify themes using the World Health Organization health system building blocks as a guiding framework. Results: Governance strategies included establishment of coordination committees and development and dissemination of guidelines. Infrastructure and commodities strategies included review of drug supply plans and allowing emergency orders. Workforce strategies included provision of infection prevention and control equipment, recruitment and provision of incentives. Service delivery modifications included designation of facilities for COVID-19 management, patient self-management, dispensing drugs for longer periods and leveraging community patient networks to distribute medicines. However, multi-month drug dispensing led to drug stock-outs while community drug distribution was associated with stigma concerns. Conclusions: Health service maintenance during emergencies requires coordination to harness existing health system investments. The service continuity committee coordinated efforts to maintain services and should remain a critical element of emergency response. Self-management and leveraging patient networks should address stigma to support service continuity in similar settings and strengthen service delivery beyond the pandemic.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

In order to shorten the detection time and improve the average precision on embedded devices, A lightweight and high accuracy model is proposed for passion fruit in complex environments (backlight, occlusion, overlap, sunny, cloudy, rainy). Firstly, replacing the backbone network of YOLOv5 with a lightweight GhostNet model reduces the number of parameters and computation while improving detection speed. Secondly, a new feature branch is added to the GhostNet network, and the feature fusion layer in the neck network is reconstructed to effectively combine the lower-level and higher-level features, which not only improves the accuracy of the model but also maintains its lightweight. Finally, the knowledge distillation methods are used to transfer the knowledge from the more capable teacher model to the less capable student model, which significantly improving the detection accuracy. The improved model is denoted as G-YOLO-NK. The average accuracy of the G-YOLO-NK network is 96.00%, which is 1.00% higher than the original YOLOv5s model. Furthermore, the improved model size is 7.14MB, reduced to half of the original model, and the real-time detection frame rate is 11.25 FPS on the Jetson Nano. Compared to the state-of-the-art model, the proposed model outperforms them in terms of average precision and detection performance. The present work provides an effective model for real-time detection of passion fruits in complex orchard scenes, which can provide valuable technical support for the development of orchard picking robots and greatly improve the intelligence level of orchards.

The impact of interaction SS with MJO on rainfall along Java Island to East Nusa Tenggara has been studied using daily rainfall observation data from 2140 weather observation stations, which are also equipped with GSMaP, OLR, and ERA5 data. There were 61 SS events found, 17 during active MJO and 44 in inactive MJO. Rainfall increases more in the western study area when the active MJO and more in the eastern study area when the inactive MJO is due to SS. SS reduces rainfall in the Jakarta region, regardless of the activity or inactivity of the MJO. SS causes extreme rainfall to only occur in a small part of certain areas, so it tends to significantly reduce the possibility of extreme rainfall. In the southern part of the IMC, SS predominates over MJO in supporting increased water vapor transport. Large-scale synoptic circulations like the monsoon, SS, and MJO can interact with local land-sea wind circulation to produce spatiotemporal variability in rainfall on Java Island. Rainfall mostly increases in the afternoon and decreases in the morning when SS occurs, whether there is MJO or not. Convective instability analysis indicates that SS increases precipitation, most likely by lowering CIN and raising VIMFC.

The Simultaneous Localization And Mapping (SLAM) scanner is an easy and portable Light Detection And Ranging (LiDAR) data acquisition device. Its main output is a 3D point cloud covering the scanned scene. Regarding the importance of accuracy in the survey domain, this paper aims to assess the accuracy of two SLAM scanners: the NavVis VLX and the BLK2GO Scanner. This assessment is conducted for both outdoor and indoor environments. In this context, two types of reference data are used: the Total Station (TS) and the static scanner Z+F Imager 5016. To carry out the assessment, four comparisons are tested: cloud to cloud, cloud to mesh, mesh to mesh, and edge detection board assessment. However, the results of the assessments confirm that the accuracy of indoor SLAM scanner measurements (5 mm) is greater than that of outdoor ones (between 10 mm and 60 mm). Moreover, the comparison of cloud to cloud provides the best accuracy regarding direct accuracy measurement without manipulations. Finally, based on the high accuracy, scanning speed, flexibility, and the accuracy differences between tested cases, it is confirmed that SLAM scanners are effective tools for data acquisition.

The practice of nurse health coaching (NHC) draws from the art and science of nursing, behavioral sciences, and evidence-based health coaching methods. This secondary analysis of the audio-recorded natural language of participants during NHC sessions of our recent 8-week RCT evaluates improvement over time in cognitive-behavioral outcomes: Change Talk, Resiliency, Self-Efficacy/Independent Agency, Insight & Pattern Recognition, and Building Towards Sustainability. We developed a measurement tool for coding, Indicators of Health Behavior Change (IHBC), that was designed to allow trained health coach experts to assess the presence and frequency of the indicators in the natural language content of participants. We used a two-step method for randomly selecting the 20-minute audio-recorded session that was analyzed at each time point. Fifty-six participants had high-quality audio recordings of the NHC sessions. Twelve participants were placed in the social determinants of health (SDH) group based on the following: low income (<$20,000/year), early-onset hypertension, and social disadvantages. Our analyses significantly improved Change Talk and the other four factors over time. Our factor analyses indicated two distinct factors at each measurement point of the study, demonstrating the stability of the outcome measures over time. Our newly developed measurement tool, IHBC, proved stable in structure over time and sensitive to change. This NHC program shows promise in improving cognitive-behavioral indicators associated with health behavior change in both non-SDH and SDH individuals.