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Bio-oil is one of the potential resources to address the sustainable energy development and environmental issues. Microwave-assisted Rapid Hydrothermal Liquefaction Process is one of the popular techniques that is used to extract bio-oil from biomass. In this paper, the bio-oil has been extracted from Palm Kernel Shells by using microwave-assisted and conventional heating pyrolysis processes. A modified heating mantle apparatus are used to conduct the experiment for extracting the bio-oil. The experiments are conducted by varying the hydrothermal temperature and time for both techniques to achieve the conversion of the bio-oil from the raw material. It is found that the yield of bio-oil for microwave-assisted Rapid Hydrothermal Liquefaction Process at 350°C and 400°C are from 10.70 wt% to 25.60 wt% within hydrothermal time 6, 9 and 12 minutes. The pH value of the bio-oil is acidic with the range from 3 to 4. The calorific value of the bio-oil is varied from 24 to 26 MJ/kg for both conversion methods. Fourier Transform Infrared Spectroscopy (FTIR) result reveals that multiple functional groups (alcohol, aldehydes, carboxylic acid and ketones) are present in the PKS bio-oil.

Implementation of coral restoration practices within reef management strategies is accelerating globally to support reef resilience and recovery. However, full costs underpinning restoration project feasibility have historically been underreported yet are critical to informing restoration cost-benefit decision-making. Such knowledge is especially lacking for Australia’s Great Barrier Reef (GBR), where a coral restoration program led by reef tourism operators, Coral Nurture Program (CNP), was initiated in 2018 (northern GBR) and continues to scale. Here we describe the early outcomes and costs of implementing similar tourism-led asexual coral propagation and outplanting practices in a new region, the Whitsundays (central GBR) through the CNP. Specifically, we detail the local operational and environmental context of CNP Whitsundays, describe the costs of implementation and continuation of restoration activities, as well as evaluate survivorship of coral outplants across three restoration sites for nine months after project establishment (August 2022 to June 2023). Baseline benthic surveys revealed relatively low hard coral cover at restoration sites (ranging from 3.22-8.67%), which significantly differed in benthic composition from coral collection sites (ranging 16.67-38.06%), supporting strong motivation by tourism operators to undertake restoration activities. Mean coral survivorship of coral outplants in fate-tracked plots differed between the three restoration sites after 267 days (ranging 23.33-47.58%), with declines largely driven by coral detachment. Early-stage cost-effectiveness (costs relative to outplant survival) associated with implementation of restoration activity varied widely from US$33.04-178.55 per surviving coral (n = 4,425 outplants) depending on whether ‘in-kind’ costs, restoration activity (outplanting only vs. total costs encompassing planning through to monitoring), site-based survivorship, or a combination of these factors, were considered. As coral reef restoration projects continue to be established globally, our results highlight the need for ongoing, long-term monitoring that can inform adaptive practice, and fully transparent cost-reporting to understand and improve feasibility for any given project. We further highlight the inherent context-dependency of restoration costs, and the importance of considering local social-environmental contexts and their associated cost-benefits in economic rationale for reef restoration projects.

Abstract The first conference of the Vaccination Acceptance Research Network, VARN2022: Shaping Global Vaccine Acceptance with Localized Knowledge, was held virtually, from March 1st to 3rd 2022. This inaugural event brought together a global representation of experts to discuss key priorities and opportunities emerging across the ecosystem of vaccine acceptance and demand, from policies to programs and practice. Convened by the Sabin Vaccine Institute, VARN aims to support dialogue among multidisciplinary stakeholders to enhance the uptake of social and behavioral science-based solutions for vaccination decision-makers and implementers. The conference centered around four key themes: 1) Understanding vaccine acceptance and its drivers; 2) One size does not fit all: community- and context-specific approaches to increase vaccine acceptance and demand; 3) Fighting the infodemic and harnessing social media for good; and 4) Frameworks, data integrity and evaluation of best practices. Across the conference, presenters and participants considered the drivers of and strategies to increase vaccine acceptance and demand relating to COVID-19 vaccination and other vaccines across the life-course and across low-, middle- and high-income settings. VARN2022 provided a wealth of evidence from around the world, highlighting the need for human-centered, multi-sectoral and transdisciplinary approaches to improve vaccine acceptance and demand. This report summarizes insights from the diverse presentations and discussions held at VARN2022, which will form a roadmap for future research, policy making, and interventions to improve vaccine acceptance and demand globally.

Using various forms of enrichment, animal care specialists encourage species-specific behaviors and discourage stereotypic behaviors. Within the zoo community, bears (Ursids spp.) are commonly housed, yet are prone to exhibiting stress-related behaviors. Here, we assess the effect of access to multiple habitats, including areas of off guest view, on the welfare of two American black bears (U. americanus) housed at the North Carolina Zoo. In this study, we looked at two behaviors, pacing and foraging to represent negative and positive welfare indicators. We performed logistic regressions to model the effect of access on these behaviors. Because having an animal visible to guests is important to consider when creating management plans, we also explored the effect of access on the bears’ visibility. We found that full access reduced the likelihood of pacing by an average of 13% and increased the likelihood of foraging by an average of 5%. Access to multiple areas reduced the probability of visibility by 57% for one individual but did not impact visibility of the other bear. This case study suggests the value of access to zoo animal welfare and should incite future research aimed at exploring the effects of access on various behavioral outcomes.

This case report describes a case of severe dysphagia lusoria secondary to an aberrant right subclavian artery causing compression of the esophagus. Our 62-year-old female patient presented with severe dysphagia and underwent right carotid–subclavian bypass with uncovered thoracic endovascular aortic repair and coil embolization of the aberrant right subclavian artery. This case is unique in that an uncovered dissection stent graft was used to avoid occluding the anatomic left subclavian artery and, therefore, avoid a left carotid–subclavian bypass. This case highlights a unique anatomic variant, its surgical repair, and the long-term improvement in the patient's quality of life.

After a decade of dolutegravir (DTG) use in various antiretroviral therapy combinations and in diverse populations globally, it is critical to identify HIV strains with reduced drug susceptibility and monitor emergent resistance in people living with HIV who experience virologic failure while on DTG-based regimens. We searched the PubMed, Embase, and Cochrane databases to identify studies that reported DTG resistance-associated mutations (RAMs) emerging under selection pressure. Our review showed that RAMs conferring resistance to DTG were rare in 2-drug and 3-drug regimens used in real-world cohorts, corroborating data from clinical trials. The potency of DTG in maintaining virologic suppression was demonstrated, even in cases of pre-existing resistance to companion drugs in the regimen. Estimates of DTG RAMs depended on the population and certain risk factors, including monotherapy, baseline resistance or lack of genotypic testing, treatment history and prior virologic failure, and suboptimal treatment adherence. The RAMs detected after virologic failure, often in heavily treatment-experienced individuals with prior exposure to integrase strand transfer inhibitors, were G118R, E138K, G140A/C/R/S, Q148H/K/R, N155H, and R263K. Overall, these data highlight the durable effectiveness and high barrier to resistance of DTG as part of combination antiretroviral therapy in a wide variety of settings.

Introduction: Medical students self-report insufficient training in topics of gender and sexuality in medicine, which may ultimately lead to negative health outcomes in patients for whom they willprovide care. This study aims to identify whether a studentinitiated lecture series on topics related to gender and sexual health leads to greater student comfort with discussing topics related to diverse sexual content.Methods: Medical students matriculated during two consecutive academic years were invited to participate in the lecture series. Investigators administered anonymous pre- and post-seriessurveys (n=152 and 105 respondents, respectively) using google forms. Respondents rated their comfort levels discussing relevant topics and provided narrative feedback concerning strengths andareas for improvement of the lecture series. Overlaps between the 95% confidence intervals around pre- and post-series percentage of students comfortable/very comfortable discussing each topicwere examined to compare pre- vs post-series comfort ratings. Narrative comments were reviewed for thematic feedback.Results: 105 medical students completed the lecture series, with 80% identifying as female. Self-assessed comfort levels across all seminar topics were greater in post- versus pre-lecture seriessurveys with the following topics showing the biggest differences (percentage of students “somewhat” or “very” comfortable [95% confidence intervals]: discussing sexuality with gender (68%[59-77] vs. 29%[22-36]) and sexual minority patients (84%[77-91] vs. 49%[41-57]), HIV prevention counseling (70%[61-78] vs. 20%[20-34]), identifying female genital cutting (44%[34-53] vs. 11%[6-16]), and discussing intimate partner violence (65%[55-74] vs. 33%[25-40]). Qualitative analysis indicated respondents found the lectures to be effective and believed they should be integrated into the required medical school curriculum. Conclusion: Our student-initiated lecture series was associated with greater student comfort discussing topics related to gender and sexuality with patients. This framework represents a usefulmethod to address gaps in medical education and has the potential to improve health outcomes in multiple populations.

Abstract Age-related macular degeneration (AMD) is the primary cause of blindness in adults over 60 years of age, and clinical trials are currently assessing the therapeutic potential of retinal pigmented epithelial (RPE) cell monolayers on implantable scaffolds to treat this disease. However, challenges related to the culture, long-term storage, and long-distance transport of such implants currently limit the widespread use of adherent RPE cells as therapeutics. Here we report a xeno-free protocol to cryopreserve a confluent monolayer of clinical-grade, human embryonic stem cell-derived RPE cells on a parylene scaffold (REPS) that yields viable, polarized, and functional RPE cells post-thaw. Thawed cells exhibit ≥ 95% viability, have morphology, pigmentation, and gene expression characteristic of mature RPE cells, and secrete the neuroprotective protein, pigment epithelium-derived factor (PEDF). Stability under liquid nitrogen (LN2) storage has been confirmed through one year. REPS were administered immediately post-thaw into the subretinal space of a mammalian model, the Royal College of Surgeons (RCS)/nude rat. Implanted REPS were assessed at 30, 60, and 90 days post-implantation, and thawed cells demonstrate survival as an intact monolayer on the parylene scaffold. Furthermore, immunoreactivity for the maturation marker, RPE65, significantly increased over the post-implantation period in vivo, and cells demonstrated functional attributes similar to non-cryopreserved controls. The capacity to cryopreserve adherent cellular therapeutics permits extended storage and stable transport to surgical sites, enabling broad distribution for the treatment of prevalent diseases such as AMD.

In C. elegans, germline ablation leads to long life span and stress resistance. It has been reported that mutations that block oogenesis or an upstream step in germline development confer strong resistance to hypoxia. We demonstrate here that the hypoxia resistance of sterile mutants is dependent on developmental stage and age. In just a 12-hour period, sterile animals transform from hypoxia sensitive L4 larvae into hypoxia resistant adults. Since this transformation occurs in animals with no germline, the physiological programs that determine hypoxia sensitivity in germline mutants occur independently of germline signals and instead rely on signals from somatic tissues. Furthermore, we found two distinct mechanisms of hypoxia resistance in germline deficient animals. First, a DAF-16/FoxO independent mechanism that occurs in all hypoxia resistant sterile adults and, second, a DAF-16/FoxO dependent mechanism that confers an added layer of resistance, or "super-resistance", to animals with no germline as they age past day 1 of adulthood. RNAseq data showed that genes involved in both cytosolic and mitochondrial protein translation are repressed in sterile adults and further repressed only in germline deficient mutants as they age. Importantly, mutation of daf-16 specifically blocked the repression of cytosolic ribosomal protein genes, but not mitochondrial ribosomal protein genes, implicating DAF-16/FoxO mediated repression of cytosolic ribosomal protein genes as a mechanism of hypoxia super-resistance. Consistent with this hypothesis, the hypoxia super-resistance of aging germline deficient adults was also suppressed by dual mutation of ncl-1 and larp-1, two regulators of protein translation and ribosomal protein abundance. These studies provide novel insight into a profound physiological transformation that takes place in germline mutants during development, showing that some of the unique physiological properties of these long-lived animals are derived from developmentally dependent DAF-16/FoxO mediated repression of genes involved in cytosolic protein translation.

Summary: This paper compares the relative cost of long-distance, large-scale energy transmission by electricity, gaseous, and liquid carriers (e-fuels). The results indicate that the cost of electrical transmission per delivered MWh can be up to eight times higher than for hydrogen pipelines, about eleven times higher than for natural gas pipelines, and twenty to fifty times higher than for liquid fuels pipelines. These differences generally hold for shorter distances as well. The higher cost of electrical transmission is primarily because of lower carrying capacity (MW per line) of electrical transmission lines compared to the energy carrying capacity of the pipelines for gaseous and liquid fuels. The differences in the cost of transmission are important but often unrecognized and should be considered as a significant cost component in the analysis of various renewable energy production, distribution, and utilization scenarios.

The live attenuated Mycobacterium bovis strain, Bacille Calmette Guérin (BCG) is a potent innate immune stimulator. In the C57BL/6 mouse model of tuberculosis, BCG vaccination leads to a significant reduction of Mycobacterium tuberculosis burden after aerogenic infection. Our studies indicated that BCG induced protection against pulmonary tuberculosis was independent of T cells and present as early as 7 days after vaccination. This protection showed longevity, as it did not wane when conventional T cell and TNF-α deficient mice were infected 30 days post-vaccination. As BCG induced mycobacterial killing after 7 days, this study investigated the contributions of the innate immune system after BCG vaccination to better understand mechanisms required for mycobacterial killing. Subcutaneous BCG inoculation resulted in significant CD11b+F4/80+ monocyte subset recruitment into the lungs within 7 days. Further studies revealed that killing of mycobacteria was dependent on the viability of BCG, because irradiated BCG did not have the same effect. Although others have identified BCG as a facilitator of trained innate immunity, we found that BCG reduced the mycobacterial burden in the absence of mechanisms required for trained innate immunity, highlighting a role for macrophages and neutrophils for vaccine induced killing of M. tuberculosis.

Preservice teachers’ views of two types of technologies which provided realistic environments in which to practice microteaching are described: (1) TLE TeachLivE™ Lab, a virtual reality environment that employs avatars as students in a virtual classroom, and (2) web conferencing technology to synchronously teach students in remotely located classrooms. Preservice teachers opined that each technology offers a relatively realistic environment that allows them to interact with virtual and real students. Microteaching through these technologies increases their self-confidence and provided a safe, non-threatening environment for them to reflect on their practice. We concluded these emerging technologies can provide viable alternatives to bringing classroom realism for preservice teachers to practice their teaching skills.

Alzheimer’s disease (AD) is characterized by progressive neurodegeneration and a concomitant loss of synapses and cognitive abilities. Recently, we have proposed that an alteration of neuronal membrane lipid microdomains increases neuronal resistance toward amyloid-β stress in cultured neurons and protects from neurodegeneration in a mouse model of AD. Lipid microdomains are highly enriched in a specific subclass of glycosphingolipids, termed gangliosides. The enzyme glucosylceramide synthase (GCS) catalyzes the rate-limiting step in the biosynthesis of these gangliosides. The present work now demonstrates that genetic GCS deletion in subsets of adult forebrain neurons significantly improves the spatial memory and counteracts the loss of dendritic spines in the hippocampal dentate gyrus of 5x familial AD mice (5xFAD//Ugcgf/f//Thy1-CreERT2//EYFP mice), when compared to 5xFAD//Ugcgf/f littermates (5xFAD mice). Aberrantly activated glial cells and their expression of pro-inflammatory cytokines have emerged as the major culprits for synaptic loss in AD. Typically, astrocytic activation is accompanied by a thickening of astrocytic processes, which impairs astrocytic support for neuronal synapses. In contrast to 5xFAD mice, 5xFAD//Ugcgf/f//Thy1-CreERT2//EYFP display a less pronounced thickening of astrocytic processes and a lower expression of tumor necrosis factor-α and interleukin 1-α in the hippocampus. Thus, this work further emphasizes that GCS inhibition may constitute a potential therapeutic target against AD.

Low cost, durable, and selective membranes with high ionic conductivity are a priority need for wide-spread adoption of polymer electrolyte membrane fuel cells (PEMFCs) and direct methanol fuel cells (DMFCs). Electrolyte membranes are a major cost component of PEMFC stacks at low production volumes. PEMFC membranes also impose limitations on fuel cell system operating conditions that add system complexity and cost. Reactant gas and fuel permeation through the membrane leads to decreased fuel cell performance, loss of efficiency, and reduced durability in both PEMFCs and DMFCs. To address these challenges, the U.S. Department of Energy (DOE) Fuel Cell Technologies Program, in the Office of Energy Efficiency and Renewable Energy, supports research and development aimed at improving ion exchange membranes for fuel cells. For PEMFCs, efforts are primarily focused on developing materials for higher temperature operation (up to 120 °C) in automotive applications. For DMFCs, efforts are focused on developing membranes with reduced methanol permeability. In this paper, the recently revised DOE membrane targets, strategies, and highlights of DOE-funded projects to develop new, inexpensive membranes that have good performance in hot and dry conditions (PEMFC) and that reduce methanol crossover (DMFC) will be discussed.

Kinase Suppressor of RAS 1 (KSR1) is a scaffolding protein for the RAS-RAF-MEK-ERK pathway, which is one of the most frequently altered pathways in human cancers. Previous results have shown that KSR1 has a critical role in mutant RAS-mediated transformation. Here, we examined the role of KSR1 in mutant BRAF transformation. We used CRISPR/Cas9 to knock out KSR1 in a BRAFV600E-transformed melanoma cell line. KSR1 loss produced a complex phenotype characterised by impaired proliferation, cell cycle defects, decreased transformation, decreased invasive migration, increased cellular senescence, and increased apoptosis. To decipher this phenotype, we used a combination of proteomic ERK substrate profiling, global protein expression profiling, and biochemical validation assays. The results suggest that KSR1 directs ERK to phosphorylate substrates that have a critical role in ensuring cell survival. The results further indicate that KSR1 loss induces the activation of p38 Mitogen-Activated Protein Kinase (MAPK) and subsequent cell cycle aberrations and senescence. In summary, KSR1 function plays a key role in oncogenic BRAF transformation.

To explore an off-season enterovirus D68 (EV-D68) upsurge in the winter season of 2019/2020, we adapted a whole-genome sequencing approach for Nanopore Sequencing for 20 hospitalized patients with accompanying respiratory or neurological presentation. Applying phylodynamic and evolutionary analysis on Nextstrain and Datamonkey respectively, we report a highly diverse virus with an evolutionary rate of 3.05 × 10 -3 substitutions per year (entire EV-D68 genome) and a positive episodic/diversifying selection with persistent yet undetected circulation likely driving evolution. While the predominant B3 subclade was identified in 19 patients, one A2 subclade was identified in an infant presenting with meningitis. Exploring single nucleotide variations using CLC Genomics Server showed high levels of non-synonymous mutations, particularly in the surface proteins, possibly highlighting growing problems with routine Sanger sequencing for typing enteroviruses. Surveillance and molecular approaches to enhance current knowledge of infectious pathogens capable of pandemic potential are paramount to early warning in health care facilities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cassidy, Lizarazo-Forero, Schuele, Van Leer-Buter and Niesters.)

Point-of-care syndromic panels allow for simultaneous and rapid detection of respiratory pathogens from nasopharyngeal swabs. The clinical performance of the QIAstat-Dx Respiratory SARS-CoV-2 panel RP2.0 (QIAstat-Dx RP2.0) and the BioFire FilmArray Respiratory panel RP2.1 (BioFire RP2.1) was evaluated for the detection of SARS-CoV-2 and other common respiratory pathogens. A total of 137 patient samples were retrospectively selected based on emergency department admission, along with 33 SARS-CoV-2 positive samples tested using a WHO laboratory developed test. The limit of detection for SARS-CoV-2 was initially evaluated for both platforms. The QIAstat-Dx RP2.0 detected SARS-CoV-2 at 500 copies/mL and had a positive percent agreement (PPA) of 85%. The BioFire RP2.1 detected SARS-CoV-2 at 50 copies/mL and had a PPA of 97%. Both platforms showed a negative percent agreement of 100% for SARS-CoV-2. Evaluation of analytical specificity from a range of common respiratory targets showed a similar performance between each platform. The QIAstat-Dx RP2.0 had an overall PPA of 82% (67-100%) in clinical samples, with differences in sensitivity depending on the respiratory target. Both platforms can be used to detect acute cases of SARS-CoV-2. While the QIAstat-Dx RP2.0 is suitable for detecting respiratory viruses within a clinical range, it has less analytical and clinical sensitivity for SARS-CoV-2 compared to the BioFire RP2.1., Competing Interests: Qiagen provided the QIAstat-Dx respiratory SARS-CoV-2 panel V2 test cartridges used in this study but did not take part on the study design, data collection, analysis, or manuscript preparation. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cassidy, van Genne, Lizarazo-Forero, Niesters and Gard.)

Chronic enterovirus infections can cause significant morbidity, particularly in immunocompromised patients. This study describes a fatal case associated with a chronic untypeable enterovirus infection in an immunocompromised patient admitted to a Dutch university hospital over nine months. We aimed to identify the enterovirus genotype responsible for the infection and to determine potential evolutionary changes. Long-read sequencing was performed using viral targeted sequence capture on four respiratory and one faecal sample. Phylogenetic analysis was performed using a maximum likelihood method, along with a root-to-tip regression and time-scaled phylogenetic analysis to estimate evolutionary changes between sample dates. Intra-host variant detection, using a Fixed Ploidy algorithm, and selection pressure, using a Fixed Effect Likelihood and a Mixed Effects Model of Evolution, were also used to explore the patient samples. Near-complete genomes of enterovirus C104 (EV-C104) were recovered in all respiratory samples but not in the faecal sample. The recovered genomes clustered with a recently reported EV-C104 from Belgium in August 2018. Phylodynamic analysis including ten available EV-C104 genomes, along with the patient sequences, estimated the most recent common ancestor to occur in the middle of 2005 with an overall estimated evolution rate of 2.97 × 10 -3 substitutions per year. Although positive selection pressure was identified in the EV-C104 reference sequences, the genomes recovered from the patient samples alone showed an overall negative selection pressure in multiple codon sites along the genome. A chronic infection resulting in respiratory failure from a relatively rare enterovirus was observed in a transplant recipient. We observed an increase in single-nucleotide variations between sample dates from a rapidly declining patient, suggesting mutations are weakly deleterious and have not been purged during selection. This is further supported by the persistence of EV-C104 in the patient, despite the clearance of other viral infections. Next-generation sequencing with viral enrichment could be used to detect and characterise challenging samples when conventional workflows are insufficient., (© The Author(s) 2022. Published by Oxford University Press.)

Enterovirus infections are known to cause a diverse range of illnesses, even in healthy individuals. However, information detailing enterovirus infections and their severity in immunocompromised patients, such as transplant recipients, is limited. We compared enterovirus infections in terms of genotypes, clinical presentation, and severity between transplant and nontransplant patients. A total of 264 patients (38 transplant recipients) with 283 enterovirus infection episodes were identified in our hospital between 2014 and 2018. We explored the following factors associated with enterovirus infections: clinical presentation and diagnosis on discharge, length of hospital stay, symptom persistence, and infection episodes in both children and adults. We observed some differences in genotypes between patients, with enterovirus group C occurring mainly in transplant recipients ( P < 0.05). EV-associated gastrointestinal infections were more common in patients with a transplant (children [71%] and adults [46%]), compared to nontransplant patients ( P < 0.05). Additionally, nontransplant patients had a higher number of hospital stays ( P < 0.05), potentially reflecting more severe disease. However, transplant patients were more likely to have symptom persistence after discharge ( P < 0.05). Finally, children and adults with a transplant were more likely to have additional enterovirus infection episodes ( P < 0.05). In our cohort, enterovirus infections did not seem to be more severe after transplantation; however, patients tended to present with different clinical symptoms and had genotypes rarely found in nontransplant recipients. IMPORTANCE Despite the high prevalence of enteroviruses in the community and the increasing demand for transplants from an aging population, knowledge on enteroviruses in solid organ transplant recipients is currently limited. Transplant recipients represent a significant patient population and require additional considerations in patient management, particularly as they have an increased risk of disease severity. Enteroviruses are known to cause significant morbidity, with a diverse range of clinical presentation from over 100 different genotypes. In this study, we aimed to provide a more comprehensive overview of enteroviral infections in transplant recipients, compared to nontransplant patients, and to bridge some gaps in our current knowledge. Identifying potential clinical manifestation patterns can help improve patient management following enterovirus infections.

The natural compound curcumin has been shown to have therapeutic potential against a wide range of diseases such as cancer. Curcumin reduces cell viability of renal cell carcinoma (RCC) cells when combined with TNF-related apoptosis-inducing ligand (TRAIL), a cytokine that specifically targets cancer cells, by helping overcome TRAIL resistance. However, the therapeutic effects of curcumin are limited by its low bioavailability. Similar compounds to curcumin with higher bioavailability, such as demethoxycurcumin (DMC) and 3,5-bis(2-fluorobenzylidene)-4-piperidone (EF24), can potentially have similar anticancer effects and show a similar synergy with TRAIL, thus reducing RCC viability. This study aims to show the effects of DMC and EF24 in combination with TRAIL at reducing ACHN cell viability and ACHN cell migration. It also shows the changes in death receptor 4 (DR4) expression after treatment with these compounds individually and in combination with TRAIL, which can play a role in their mechanism of action.

The Decision component of the Activation-Decision-Construction-Action-Theory (ADCAT) utilizes a cost-benefit formula to explain the cognitive, motivational and social processes involved in deception. Three prior studies suggest that ADCAT can be used to predict adults' future deceptive behavior; however, no study has assessed the potential relevance of ADCAT with children. The present study is the first to date to examine whether this cost-benefit formula can predict children's hypothetical decisions to tell three types of lies, and whether there are specific developmental factors that need to be considered. The results indicate that the cost-benefit formula was only effective for predicting children's hypothetical lies for self-gain at no cost to another (Self-No Cost lies) and lies for others when there was a personal cost (Other-Cost to Self). More specifically, expected value of telling the truth was related to lower willingness to tell hypothetical Self-No Cost and Other-Cost to Self lies. On the other hand, the expected value of lying was not related to children's hypothetical decisions to tell Self-No Cost, Self-Cost to Other or Other-Cost to Self lies. Children's inhibitory control and theory of mind were significant covariates for some of the ADCAT predictor variables and children's hypothetical truth and lying behaviors. Altogether, these findings indicate that the effectiveness of the ADCAT cost-benefit formula for predicting children's lying behavior is affected by developmental factors and the type of lie being analyzed., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Amitriptyline is prescribed to reduce the intensity of chronic neuropathic pain. There is a paucity of validated in vivo evidence in humans regarding amitriptyline's mechanism of action. We examined the effect of amitriptyline therapy on cerebrospinal fluid (CSF) neuropeptides and proteome in patients with chronic neuropathic pain to identify potential mechanisms of action of amitriptyline., Methods: Patients with lumbar radicular neuropathic pain were selected for inclusion with clinical and radiological signs and a >50% reduction in pain in response to a selective nerve root block. Baseline (pre-treatment) and 8-week (post-treatment) pain scores with demographics were recorded. CSF samples were taken at baseline (pre-treatment) and 8 weeks after amitriptyline treatment (post-treatment). Proteome analysis was performed using mass spectrometry and secreted cytokines, chemokines and neurotrophins were measured by enzyme-linked immunosorbent assay (ELISA)., Results: A total of 9/16 patients experienced a >30% reduction in pain after treatment with amitriptyline and GO analysis demonstrated that the greatest modulatory effect was on immune system processes. KEGG analysis also identified a reduction in PI3K-Akt and MAPK signalling pathways in responders but not in non-responders. There was also a significant decrease in the chemokine eotaxin-1 (p ​= ​0.02) and a significant increase in the neurotrophin VEGF-A (p ​= ​0.04) in responders., Conclusion: The CSF secretome and proteome was modulated in responders to amitriptyline verifying many pre-clinical and in vitro models. The predominant features were immunomodulation with a reduction in pro-inflammatory pathways of neuronal-glia communications and evidence of a neurotrophic effect., Competing Interests: The authors have no conflict of interest to declare., (© 2020 The Author(s).)

Shotgun metagenomic sequencing (SMg) enables the simultaneous detection and characterization of viruses in human, animal and environmental samples. However, lack of sensitivity still poses a challenge and may lead to poor detection and data acquisition for detailed analysis. To improve sensitivity, we assessed a broad scope targeted sequence capture (TSC) panel (ViroCap) in both human and animal samples. Moreover, we adjusted TSC for the Oxford Nanopore MinION and compared the performance to an SMg approach. TSC on the Illumina NextSeq served as the gold standard. Overall, TSC increased the viral read count significantly in challenging human samples, with the highest genome coverage achieved using the TSC on the MinION. TSC also improved the genome coverage and sequencing depth in clinically relevant viruses in the animal samples, such as influenza A virus. However, SMg was shown to be adequate for characterizing a highly diverse animal virome. TSC on the MinION was comparable to the NextSeq and can provide a valuable alternative, offering longer reads, portability and lower initial cost. Developing new viral enrichment approaches to detect and characterize significant human and animal viruses is essential for the One Health Initiative.

Unfortunately, the author names in the author group section were incorrectly captured in the published online paper.