In two sequential replicates (n=90 and n=96 feedlot finisher cattle, respectively) we measured the impact of an Enterococcus faecium-based probiotic (DFM) and an altered feedlot pen environment on antimicrobial resistance among fecal enterococci in cattle fed (or, not fed) the macrolide tylosin. Diluted fecal samples were spiral-plated on plain and antibiotic-supplemented m-Enterococcus agar. In the first replicate, tylosin significantly (p<0.05) increased the relative quantity of erythromycin-resistant enterococci. This effect was diminished in cattle fed the DFM in conjunction with tylosin. A similar observed effect was not statistically significant (P > 0.05) in the second replicate. Isolates were speciated and resistance phenotypes were obtained for E. faecium and E. hirae. E. faecium isolates were whole-genome sequenced, which yielded sequence types (ST), resistance genes and phylogeny. Samples of the DFM were sequenced and found to contain E. faecium ST296, which was not present on Day 0 of either replicate. This DFM sequence type was found in fecal samples after Day 0, the majority of which were isolated from cattle in one of the DFM-fed pens. Increased prevalence of ST296 occurred with a concomitant decrease in ST240; of importance, the latter typically harbored both ermB and tet(M) genes.

Antimicrobial resistance (AMR) represents a growing crisis in both human and veterinary medicine. We evaluated the use of two categories of antibiotic alternatives – heavy metals and essential oils – in beef cattle, and their effects on gram-negative and gram-positive bacteria. In this randomized controlled field trial, we measured the impact of supplemental zinc and menthol on antimicrobial resistance among commensal enteric bacteria of feeder cattle. Fecal suspensions were plated onto plain- and antibiotic-supplemented MacConkey and m-Enterococcus agar for quantification of total and antimicrobial-resistant Escherichia coli and Enterococcus spp., respectively. Temporal effects on overall E. coli growth were significant (P< 0.05); however, there were no significant effects on antibiotic-supplemented agar. Zinc was associated with significant increases in growth on erythromycin-supplemented m-Enterococcus agar. Cattle fed zinc exhibited significantly higher macrolide resistance among fecal enterococci isolates.

This study aims to assess using a smartphone app (DecibelX), as a noise measuring alternative to the more costly traditional use of measuring noise levels with a Sound Level Meter (SLM). The study compares the accuracy of the app to readings taken with a SLM and dosimeter, and also evaluates the app’s performance for pure tone and narrow band noise. And a usability study identifies strengths and weaknesses related to usability of the app.

In recent years, it has become common for individuals to juggle employment and unpaid care work. This is just as true for the England-based academic workforce, our focus in this article. We discuss how, in the context of English HE, support for carers is enacted and negotiated through policies and practices of care. Our focus on academics with a diverse range of caring responsibilities is unusual insofar as the literature on care in academia is overwhelmingly concerned with parents, usually mothers. The article is informed primarily by critical and post-structuralist feminist perspectives. We draw on a corpus of 47 interviews conducted with academics representing a broad range of caring responsibilities, subjects, and positions. A thematic analysis reveals how carers’ relationship with the provision and policies of care support at institutional level is characterised by ambiguity. On the one hand, participants approve of societal and institutional policy support for carers. On the other hand, they are often reluctant to position themselves as the beneficiary of such policies, expressing instead a general preference for support from outside the workplace or for workplace-based inter-individual and informal care arrangements. This resistance is particularly noticeable in the case of participants with caring responsibilities other than the parenting of healthy, able-bodied children and of those whose gender, class, racial, or sexual identity do not conform with the figure of the ‘ideal academic’, contributing to their othering in the academic realm. These findings have significant implications for policies supporting carers, pointing to the need for greater visibility and recognition of caring responsibilities in academia, especially in terms of their diverse identities.

There is a growing body of evidence supporting the significant role of bacterial biofilms in the pathogenesis of various human diseases including cancer. Biofilms are polymicrobial communities enclosed within an extracellular matrix composed of polysaccharides, proteins, extracellular DNA, and lipids. This complex matrix provides protection against antibiotics and host immune responses, enabling the microorganisms to establish persistent infections. Moreover, biofilms induce anti-inflammatory responses and metabolic changes in the host, further facilitating their survival. Many of these changes are comparable to those observed in cancer cells. This review will cover recent research on the role of bacterial biofilms in carcinogenesis, especially in colorectal (CRC) and gastric cancers, emphasizing the shared physical and chemical characteristics of biofilms and cancer. This review will also discuss the interactions between bacteria and the tumor microenvironment, which can facilitate oncogene expression and cancer progression. This information will provide insight into developing new therapies to identify and treat biofilm-associated cancers, such as utilizing bacteria as delivery vectors, using bacteria to upregulate immune function, or more selectively targeting biofilms and cancer for their shared traits.

The twospotted spider mite, Tetranychus urticae and the western tarnished plant bug, Lygus hesperus are major arthropod pests of strawberries in California. Other important insect pests include the greenhouse whitefly, Trialeurodes vaporariorum and the western flower thrips, Frankliella occidentalis. Chemical pesticides play a major role in managing these pests, but not without the associated risk of pesticide resistance and environmental safety. Two field studies were conducted in Santa Maria to evaluate the potential of botanical and microbial pesticides in the integrated pest management (IPM) of strawberry. Chemical, botanical, and microbial pesticides were evaluated against T. urticae in a small plot study in 2013 and against L. hesperus and other insect pests in a large plot study in 2015 in commercial strawberry fields. Bug vacuums were also used in the 2015 study. Results demonstrated that non-chemical alternatives can play an important role in strawberry IPM.

Alzheimer’s disease (AD) is an age-related neurodegenerative disease and is clinically characterized by cognitive impairment, memory loss, and personality disorder. Oligomers of amyloid beta-peptides (Aβ) and enhanced oxidative stress in senile plaques are prevalent pathologic hallmarks of AD. In this study, we detected the behavioral performance of Lycium ruthenicum Murray anthocyanin (LRA) -treated rats using the Morris water maze test and then investigated the effect of LRA on oxidative damage, neuronal apoptosis, and inflammatory response induced by Aβ1–42. Our results showed that LRA treatment markedly ameliorated the behavioral performance of Aβ1–42-induced rats and reduced the level of malondialdehyde, formation of protein carbonyl, and 8-hydroxy-2’-deoxygua-nosine. Furthermore, LRA also inhibited activated astrocytes and neuroinflammation via suppression of glial fibrillary acidic protein and tumor necrosis factor-alpha in the hippocampus of Aβ1–42-treated rat brain. These data suggest that LRA could be a potential anti-oxidant and anti-neuroinflammatory agent for the treatment of AD.

It is becoming clear that in addition to gap junctions, playing a role in cell-cell communication, gap junction proteins, connexins, located in cytoplasmic-compartments may have other important functions. Mitochondrial connexin 43 (Cx43) is increased after ischemic preconditioning and has been suggested to play a protective role in the heart. How Cx43 traffics to the mitochondria and the interactions of mitochondria with other Cx43-containing structures are unknown. In this study, immunocytochemical, super-resolution and transmission electron microscopy were used to detect cytoplasmic Cx43-containing structure and to demonstrate their interactions with other cytoplasmic organelles. The most prominent cytoplasmic Cx43-containing structures, annular gap junctions, were demonstrated to form intimate associations with lysosomes as well as with mitochondria. Surprisingly, the frequency of associations between mitochondria and annular gap junctions was greater than that between lysosomes and annular gap junctions. The benefits of annular gap junction/mitochondrial associations are not known. However, it is tempting to suggest that the contact between annular gap junction vesicles and mitochondria facilitates Cx43 deliver to the mitochondria. Furthermore, it points to the need for investigating trafficking of Cx43 to cytoplasmic compartments and annular gap junction as more than only a vesicle destined for degradation.

Acute pancreatitis (AP) is an inflammatory condition of the pancreas and is one of the most common ailments of the gastrointestinal system that results in significant morbidity and mortality. The main etiologic causes of AP are alcohol consumption, gallstones, hypertriglyceridemia, and biliary stones. The clinical signs and symptoms, and diagnostic criteria of AP are well established in the literature and multiple studies. Multiple scoring systems have been used to predict the severity, prognosis, and mortality associated with AP. The present review of the literature brings to light the significant and recent contributions in the etiology, risk factors, epidemiology, diagnosis, complications, prognosis and newest modalities in treatment that could be beneficial in the management of AP.

Background: Portable oxygen concentrators (POCs) have shown efficacy in delivering adequate oxygen for various patient scenarios; however, there is a lack of research on POCs’ efficacy across different respiratory rates specifically among COPD patients. Methods: This bench study was conducted using the IngMar Medical Active Servo Lung 5000 attached to flexible tubing, which simulated an adult patient’s nares. An oxygen analyzer (Maxtec Handi+) was connected to the tubing 6 inches below the nares to estimate the inspired oxygen concentration at the adult trachea. A standard nasal cannula was placed in the simulated patient nares, which was also attached to each POC. The IngMar Lung was programmed to simulate a COPD patient at the following respiratory rates: 15, 20, 30, and 40 breaths/min. POC devices were then compared to an oxygen wall outlet and a standard oxygen concentrator (non-portable CAIRE device). The POCs included the CAIRE FreeStyle Comfort (with Autosat), CAIRE FreeStyle Comfort (without Autosat), Inogen G4, Inogen G5, Phillips SimplyGo Mini, GCE Zen-O lite, Drive Medical iGo2, and Kingon POCs. Descriptive statistics and ANOVAs were computed to determine statistically significant differences between POCS and control devices (wall oxygen and standalone oxygen concentrator). Results: Across most respiratory rate scenarios, the wall oxygen and standalone oxygen concentrator (control group) resulted higher oxygen measurements compared to the POCs. Among the POCs on setting 2, the highest oxygen measurement for 15, 30, and 40 breaths/min was the CAIRE FreeStyle Comfort with AutoSat on sensitivity 5 (24.43%, 24.81%, and 25.0%, respectively). On setting 2, the 20 breaths/min highest oxygen measurement was the Inogen G4 (24.43%). For setting 5, the highest oxygen measurement for 15 breaths/min and 40 breaths/min was the CAIRE FreeStyle Comfort without AutoSat (31.56% and 26.13%, respectively), while the highest oxygen measurement for 20 breaths/min was the Inogen G5 (30.26%), and the highest oxygen measurement for 30 breaths/min was the CAIRE FreeStyle Comfort with AutoSat on sensitivity level 5 (27.89%). Conclusions: The oxygen administered through the wall and the standalone CAIRE oxygen concentrator all delivered higher oxygen levels compared to the POCs (with the exception of the 40 breaths/min scenario on setting 2). However, among the POCs, the CAIRE Freestyle Comfort with AutoSat, CAIRE Freestyle Comfort without AutoSat, and the Inogen G4 all performed the best among the various breathing rate scenarios.

Background: Disability and caste are two different forms of oppression, however Dalits and people with disabilities commonly face similar types of marginalities. Dalit women with disabilities may experience double discrimination because of the intersectionality of disability and caste. This study examines whether the disability and caste identity of women together affects and compounds the utilization of maternal healthcare services. Methods: A cross-sectional survey was conducted using a semi-structured questionnaire among a total of 354 Dalit and non-Dalit women, with and without a disability aged between 15 – 49 years. Maternal healthcare service utilization was assessed by Ante-Natal Care (ANC), health facility (HF) delivery, and Post-Natal Care (PNC) during the last pregnancy. Logistic regression was performed to detect the predictors of service utilization and identify whether disability and caste were associated with service utilization. First, disability and caste were fitted separately in models. Secondly, the intersectionality of disability and caste was tested by the inclusion of disability*caste interaction term. Finally, the confounding effect of socio-demographic factors was investigated. Results: Out of surveyed women, 73% had 4+ ANC visits, 65% had HF delivery and 29% had a PNC visit during their last pregnancy. Women with a disability had lower odds of HF delivery (OR 0.50, CI 0.30 – 0.84) and PNC (OR 0.47, CI 0.25 – 0.88) than women without a disability. Adjustment for women’s age and household wealth explained associations in HF delivery by women with disabilities. There was no association between caste and service utilization. Disability overrode caste and there was no other evidence of effect modification by women’s caste status in the utilization. However, a weak interaction effect in the utilization of ANC services was found in the caste group by their education (OR 0.19, 95% CI 0.05 – 0.74). Conclusions: Disabled women – whether Dalit or non-Dalit - had lower rates of utilizing all maternal healthcare services than non-disabled women. However, Dalit women with disabilities were more likely to receive PNC than non-Dalit women with disabilities. Increasing equity in maternal healthcare service utilization requires that traditional approaches to service development and program intervention to be re-examined and more nuanced interventions considered to ensure improved access and outcome among all vulnerable groups.

To contain and mitigate the coronavirus (COVID-19) pandemic, African governments have implemented non-pharmacological interventions (NPIs), such as imposing travel bans, confining people to their homes and closing schools, shops and workplaces. These NPIs are likely to be less effective in circumstances where people need to leave their homes to work, collect food, water and cooking fuel or where people cannot maintain distancing due to overcrowded living environments. Using data from the nationally representative South African General Household Survey 2019, we examined individuals’ vulnerability to the risk of COVID-19 infection due to their health, socioeconomic and living circumstances. We explored socioeconomic-related inequalities in COVID-19 using concentration curve and concentration index methods. Our results showed that vulnerability to COVID-19 was disproportionately concentrated among those with low socioeconomic status. Using the Recentered Influence Function decomposition approach, we found that higher income and education had a significant and positive impact on reducing socioeconomic-related COVID-19 vulnerability. Conversely, people with lower socioeconomic status were more likely to live in circumstances that made compliance with NPI requirements almost impossible, and they were also more likely to have pre-existing health conditions that made them more vulnerable to COVID-19.

Current global commitments to reduce emissions of greenhouse gases encourage national targets for renewable generation. Due to its small land mass, offshore wind could help Bahrain to fulfill its obligations. However, no scoping study has yet been carried out. The methodology presented here addresses this research need. It employs Analytical Hierarchy Process and pairwise comparison methods in a Geographical Information Systems environment. Publicly available land use, infrastructure and transport data are used to exclude areas unsuitable for development due to physical and safety constraints. Meteorological and oceanic opportunities are ranked, then competing uses are analyzed to deliver optimal sites for wind farms. The potential annual wind energy yield is calculated by dividing the sum of optimal areas by a suitable turbine footprint, to deliver maximum turbine number. Ten favourable wind farm areas were identified in Bahrain’s territorial waters, representing about 4% of the total maritime area, and capable of supplying 2.68 TWh/yr of wind energy or almost 10% of the Kingdom’s annual electricity consumption. Detailed maps of potential sites for offshore wind construction are provided in the paper, giving an initial plan for installation in these locations.

This study investigates the relationship between housing prices and vacancy rates in Hong Kong, offering insights distinct from previous cross-sectional analyses. Addressing limitations in data availability and methodological approaches, the study examines annual data spanning multiple housing size categories to uncover nuanced dynamics in the housing market. Two major contributions emerge: firstly, the analysis reveals the price elasticity of vacancy, elucidating how housing prices respond to changes in vacancy rates over time. Secondly, by considering housing vacancy changes as outcomes of the interactions between supply and demand, the study challenges the conventional independence assumption between these variables. The results support the hypothesis that housing vacancies exert a negative impact on housing prices, holding other factors constant. These findings have significant implications for policymakers, urban planners, and real estate investors, providing valuable insights for crafting targeted interventions and informing investment decisions.

The COVID-19 pandemic has highlighted the vitalness of telehealth in our medical world, where considering a restructuring of healthcare services has become paramount. In fact, telemedicine has recently earned a valuable place in many specialties; and its implications in cardiology and cardiovascular medicine were among the leading interests. In this letter, we gathered previous evidence supporting the merit of telemedicine in the fields of cardiology and cardiovascular medicine—medical branches in which patients require meticulous care and continuous monitoring—as well as protrusions of concerns about the uncertainty regarding the efficacy of telemedicine’s future implications and technologies. In sum, in the context of this still on-going pandemic, medical institutions must strive to improve telehealth technologies and implement solid future research directions in this growing field—to be able to persevere in meeting the needs of the patients. As long as no conclusive evidence exists regarding the fields where telemedicine is most worthwhile, healthcare systems will always keep the dread of wasting resources on developing ineffective programs. We conclude that telemedicine has been attributed a considerable attention in managing cardiac and cardiovascular conditions; nevertheless, further studies with solid designs are still needed to confirm its validity and utility in those specialties.

A key response to glucose stress is an increased production of unsaturated fatty acids to balance the increase of saturated fatty acids in the membrane. The C. elegans homolog of stearoyl-CoA desaturase, FAT-7, introduces the first double bond into saturated C18 fatty acids yielding oleic acid and is a critical regulatory point for surviving cold and glucose stress. Here, we incorporated 13C stable isotopes into the diet of nematodes and quantified the 13C-labelled fatty acid by GC-MS and HPLC/MS-MS to track the metabolic response to various concentrations of glucose. Previous work has analyzed membrane composition of C. elegans when responding to mild glucose stress and showed few alterations in overall fatty acid composition in the membrane. Here, in nematodes exposed to higher concentrations of glucose, a specific reduction of oleic acid and linoleic acid was observed. Using time courses and stable isotope tracing, the response of fatty acid me-tabolism to increasing levels of glucose stress has been characterized, revealing a funneling of monounsaturated fatty acids to preserve polyunsaturated fatty acid abundance. Taken together, higher levels of glucose unveil a specific reduction of oleic and linolenic acid in the metabolic re-wiring required to survive glucose stress.

Urolithins (e.g., UroA and B) are gut microbiota-derived metabolites of the natural polyphenol ellagic acid. Urolithins are associated with various health benefits, including attenuation of inflammatory signaling, anti-cancer effects and repression of lipid accumulation. The molecular mechanisms underlying the beneficial effects of urolithins remain unclear. We hypothesize that some of the human health benefits of urolithins are mediated through the aryl hydrocarbon receptor (AHR). Utilizing a cell-based reporter system, we tested urolithins for the capacity to modulate AHR activity. Cytochrome P450 1A1 (CYP1A1) mRNA levels were assessed by real-time quantitative polymerase chain reaction. Competitive ligand binding assays were performed to determine whether UroA is a direct ligand for the AHR. Subcellular AHR protein levels were examined utilizing immunoblotting analysis. AHR expression was repressed in Caco-2 cells by siRNA transfection to investigate AHR-dependency. UroA and B were able to antagonize 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced AHR-mediated transcriptional activity. Furthermore, UroA and B attenuated TCCD-mediated stimulation of CYP1A1 mRNA levels. In addition, competitive ligand binding assays characterized UroA as a direct AHR ligand. Consistent with other AHR antagonists, UroA failed to induce AHR retention in the nucleus. AHR is necessary for UroA-mediated attenuation of cytokine-induced interleukin 6 (IL6) and prostaglandin-endoperoxide synthase 2 (PTGS2) expression in Caco-2 cells. Here we identified UroA as the first dietary-derived human selective AHR antagonist produced by the gut microbiota through multi-step metabolism. Furthermore, previously reported anti-inflammatory activity of UroA may at least in part be mediated through AHR.

This study investigated the adaptability of Dunaliella salina to different salinity levels, with emphasis on growth, pigment concentration, and desalination potential. It was found that among the 21 salinity levels, salinity 75 produced consistently favorable results in cell count (13.08 x 10³ ± 1.41 x 10³ cells/mL), dry biomass (2.46 ± 0.06 g/L), pigment content (chlorophyll a = 97.5 ± 0.1 µg/L, chlorophyll b = 123.6 ± 0.3 µg/L), and desalination (9.32 ± 0.47 reduction). Therefore, salinity 75 was selected for the final trial (scale-up), which revealed unanticipatedly high cell counts (58.96 x 10³ ± 535.22 cells/mL), with dry biomass weight being statistically different (higher) than the expected (4.21 ± 0.02 g/L) (p<0.0001), most likely due to high cell count and energy reserve storage for high salinity adaption in the form of bio-compounds. Pigment growth continued (chlorophyll a = 95.4 ± 2.2 µg/L, chlorophyll b = 128.1 ± 5.1 µg/L), indicating pigment production under salt stress. Notably, desalination did not occur in this stage, possibly due to the necessity for a bigger initial inoculate, prolonged exposure or bioaccumulation becoming the prevailing mechanism over desalination. Nevertheless, the trial highlights D. salina's strong adaptation to various salinity levels. This suggests a promising future in halophyte research, particularly in understanding the mechanisms that prevent salt accumulation in cells and how to overcome this barrier. Additionally, these results suggest that microalgae could be a viable resource in saline-rich environments unsuitable for conventional agriculture, promoting industrial adaptation to adverse conditions.

There is mounting evidence that patients with severe COVID-19 disease may have symptoms that continue beyond the acute phase, extending into the early chronic phase. Often referred to as 'Long COVID'. Simultaneously, case investigations have shown that COVID-19 individuals might have a variety of neurological problems. The accurate and accessible assessment of cognitive function in patients post COVID-19 infection is thus of increasingly high importance for both public and individual health. Little is known about the influence of COVID-19 on the general cognitive levels but more importantly, at sub functions level. Therefore, we first aim to summarize current level of evidence supporting a negative impact of COVID-19 infection on cognitive functions. 27 studies have been included in the systematic review representing a total of 94,103 participants (90,317 COVID-19 patients and 3,786 healthy controls). We then performed a meta-analysis summarizing the results of 5 studies (959 participants, 513 patients) to quantify the impact of COVID-19 on cognitive functions. The overall effect, expressed in Standardized Mean Differences, is -0.56 [95%CI -0.79 ; -0.34]. To prevent disability, we finally discuss the different approaches available in rehabilitation to help these patients and to avoid long-term complication.

This study evaluated the microbial safety of vended boiled, pasteurized and UHT milk sold in Nakawa, Kampala-Uganda. 15 milk samples were analyzed; 2 samples had Salmonella, 5 had S. aureus with a count of 1.66 0.02 log₁₀CFU/ml. E. coli was detected in 8 samples with 1.0 0.02 to 3.0 0.01log₁₀CFU/ml count. A high load of 3.0 CFU/ml was obtained in 3 samples with E. coli. Four E. coli positive samples had a contamination load of 2.0 0.015log₁₀ CFU/ml of which one was pasteurized milk. Only a pasteurized milk showed a low E. coli load at 1.0 0.02log₁₀ CFU/ml. All UHT milk had no microbial contamination. Both boiled and pasteurized milk had Salmonella, S. aureus and E. coli in levels above the set threshold limits. Milk consumers in Nakawa stand a potential public health risk of food poisoning reflected by presence of Salmonella, S. aureus and E. coli in some milk sold in the area.

Far-red fluorescent reporter genes can be used for tracking cells non-invasively in vivo using fluorescence imaging. Here, we investigate the effectiveness of the far-red fluorescent protein, E2-Crimson (E2C), for tracking mouse embryonic cells (mESCs) in vivo following subcutaneous administration into mice. Using a knock-in strategy, we introduced E2C into the Rosa26 locus of an E14-Bra-GFP mESC line, and after confirming that the E2C had no obvious effect on the phenotype of the mESCs, we injected them into mice and imaged them over 9 days. The results showed that fluorescence intensity was weak, and cells could only be detected when injected at high densities. Furthermore, intensity peaked on day 4 and then started to decrease, despite the fact that tumour volume continued to increase beyond day 4. Histopathological analysis showed that although E2C fluorescence could barely be detected in vivo at day 9, analysis of frozen sections indicated that all mESCs within the tumours continued to express E2C. We hypothesise that the decrease in fluorescence intensity in vivo was probably due to the fact that the mESC tumours became more vascular with time, thus leading to increased absorbance of E2C fluorescence by haemoglobin. We conclude that the E2C reporter has limited use for tracking cells in vivo, at least when introduced as a single copy into the Rosa26 locus.

A sense of crisis pervaded the university sector as Covid-19 spread, with worries about possible significant loss of income and students in its wake. This analysis examines several years of financial and student data through the pandemic (2020-2022) for Scottish universities. It shows that far from losing money or students, universities in Scotland gained both, and accelerated income growth during Covid. The University of Glasgow stands out not only among Scottish universities but also in the Russell Group in increasing income and student numbers faster than other institutions, becoming over the course of the pandemic, the third largest university in the UK and the largest in Scotland by student numbers. The driver of income growth for all Scottish universities is expanded intakes of international students, who primarily come from Asia and Africa. Across 2021 and 2022, Scottish Universities earned income totalling £1.7 billion from international tuition fee alone. Universities across the UK are increasingly dependent on yet continuing to actively pursue international tuition fees as a primary source of income. This paper documents the situation for Scotland, considering the implications of this growth trajectory in terms of: concentrating financial dependence on a single income source; rising casualisation of staff as a means of managing higher student numbers; impacts on learning and working conditions as students numbers rapidly expand; a shifting composition of students in higher education. It concludes with reflections on: a blurring boundary between the practices and values of profit-making companies and those of the charitable university sector; the ethical and colonial implications in international student recruitment and targeting of ‘new markets’ in the Global South; and the implications of all this for the shape, health and purpose of the university sector in Scotland.

Over half of adult Americans now have diabetes or prediabetes and worse, this epidemic is now world-wide and shows no signs of slowing, with rates of both diabetes and diabetes-related health complications still rising. When advising patients with diabetes on food choices, many providers rely on nutrition guidelines provided by the American Diabetes Association (ADA), and these guidelines influence other recommendations across the globe. Given the alarming trends in diabetes, it is paramount to review the treatment guidelines to ensure they are based on rigorous and accepted scientific methods. Our review included the evidence cited by the ADA in support of its claims and recommendations for eating patterns to combat diabetes (see Description of Eating Patterns, Supplemental Appendix), as presented in the most current edition of the annual ADA’s Standards of Medical Care in Diabetes (2018 Standards). Our review also includes sources cited in the latest edition of the ADA’s Nutrition Therapy Recommendations for Adults with Diabetes (2014 Recommendations), which also informed the 2018 Standards. In October 2018 low carbohydrate was named as a recommended eating pattern by the ADA and European Association for the Study of Diabetes (EASD)⁵but only citations from the 2014 and early 2018 ADA documents were reviewed.

Introduction: Lung cancer remains a global health concern, with non-small cell lung cancer (NSCLC) comprising the majority of cases. Early detection of lung cancer has led to an increased number of cases identified in the earlier stages of NSCLC. This required the revaluation of the NSCLC treatment approaches for early-stage NSCLC. Methods: We conducted a comprehensive search using multiple databases to identify relevant studies on treatment modalities for early-stage NSCLC. Inclusion criteria prioritized but were not limited to, clinical trials and meta-analyses on surgical approaches to early-stage NSCLC conducted from 2021 onwards. Discussion: Minimally invasive approaches, such as VATS and RATS, along with lung resection techniques, including sublobar resection have emerged as treatments for early-stage NSCLC. Ground-glass opacities (GGOs) hve shown prognostic significance, especially when analyzing the consolidation-tumor ratio (CTR). There have also been updates on managing GGOs, including the non-surgical approaches, the extent of lung resection indicated, and the level of lymphadenectomy required. Conclusion: The management of early-stage NSCLC requires further assessment of treatment strategies. This includes understanding the required extent of surgical resection, interpreting the significance of GGOs (specifically GGOs with a high CTR), and evaluating the efficacy of alternative therapies. Customized treatment involving surgical and non-surgical interventions is essential for advancing patient care.

The successive steps of the oxidation mechanism of crocin, major compound of saffron, by the free OH• radical are investigated by the pulse radiolysis, steady-state (gamma) radiolysis methods and molecular simulations. The optical absorption properties of the transient species and their reaction rate constants are determined. The absorption spectrum of the oxidized radical of crocin resulting from the H-abstraction presents a maximum at 678 nm and a band at 441 nm, almost as intense as that of crocin. The spectrum of the covalent dimer of this radical contains an intense band at 441 nm and a weaker one at 330 nm. The final oxidized crocin, issued from radical disproportionation, absorbs weaker with a maximum at 330 nm. The molecular simulation results suggest that the OH• radical is electrostatically attracted by the terminal sugar and is scavenged predominantly by the neighbor methyl site of the polyene chain as in a sugar-driven mechanism. Based on detailed experimental and theoretical investigations, the antioxidant properties of crocin are highlighted.

Australia and New Zealand have the highest incidence of skin cancer. Sport is a fundamental part of Australasian culture, beginning in childhood, often with life-long participation. Participating in outdoor sports can contribute significantly to the lifetime ultraviolet radiation (UVR) dose individuals receive and their risk of developing skin cancer. This systematic scoping review explores the use of sun-protection by outdoor sporting participants in Australasia and considers how sun-protection practices may be better evaluated and improved in the community. A search of electronic databases using the search strategy “sun protection” AND “sport” AND “Australia” yielded 17 studies published in English from January 1992 to August 2021. Study methods included using UV-dosimeters to measure individual UVR-exposure; remote estimates of clothing-adjusted UVR-exposure; direct observation of sun-protection practices; and self-reported sun-exposure and sun-protection. Despite 40-years of ‘Slip Slop Slap’ campaigns in Australia, the use of sun-protection in most outdoor sports is inadequate. The paucity of comparable data limited our analyses, demonstrating a need for standardized, objective evaluation tools. Such tools, if used across a range of sports, should inform the development of workable recommendations that sporting clubs could implement and adopt into policy, thus empowering them to better protect the health of their participants.

The aim of our study is to utilise longitudinal and representative national data to explore the extent that the association between the fast food environment and overweight in adolescents is confounded by neighbourhood deprivation. Longitudinal data from the Millennium Cohort Study for England were obtained for waves 5 (ages 11/12; 2011/12; n=13,469) and 6 (ages 14/15; 2014/15; n=11,884). Our outcome variable was overweight/obesity defined using age and sex-specific International Obesity Task Force cut points. Individuals were linked, based on their residential location, to data on the density of fast food outlets and neighbourhood deprivation. Structural Equation Models were used to model associations at both ages and explicitly test for confounding. While we found some evidence for an association between the number of fast food outlets and overweight, any associations disappeared following accounting for the confounding nature of neighbourhood deprivation. Neighbourhood deprivation was consistently associated to overweight, with adolescents who resided in deprived areas more likely to be overweight. Results were largely consistent depending on different methodological decisions. Our findings suggest that policy efforts should prioritise focusing on tackling the social determinants of excess body mass which will be more effective than interventions aimed at the built environment.

Loss-of-function mutations of the spermine synthase gene (SMS) result in Snyder-Robinson Syndrome (SRS), a recessive X-linked syndrome characterized by intellectual disability, osteoporosis, hypotonia, speech abnormalities, kyphoscoliosis, and seizures. As SMS catalyzes the biosynthesis of the polyamine spermine from its precursor spermidine, SMS deficiency causes a lack of spermine with an accumulation of spermidine. As polyamines, spermine and spermidine play essential cellular roles that require tight homeostatic control to ensure normal cell growth, differentiation, and survival. Using patient-derived lymphoblast cell lines, we sought to comprehensively investigate the effects of SMS deficiency on polyamine homeostatic mechanisms including polyamine biosynthetic and catabolic enzymes, derivatives of the natural polyamines, and polyamine transport activity. In addition to decreased spermine and increased spermidine in SRS cells, ornithine decarboxylase activity and its product putrescine were significantly decreased. Treatment of SRS cells with exogenous spermine revealed that polyamine transport was active, as the cells accumulated spermine, decreased their spermidine level, and established a spermidine-to-spermine ratio within the range of wild type cells. SRS cells also demonstrated elevated levels of tissue transglutaminase, a change associated with certain neurodegenerative diseases. These studies form a basis for further investigations into the leading biochemical changes and properties of SMS-mutant cells that potentially represent therapeutic targets for the treatment of Snyder-Robinson Syndrome.

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS) characterized by varying degrees of demyelination of uncertain etiology, and is associated with specific environmental and genetic factors. Upon recognition of CNS antigens, the immune cells initiate an inflammatory process which leads to destruction and deterioration of the neurons. Innate immune cells such as macrophages, dendritic cells and natural killer cells are known to play critical roles in the pathogenesis of MS. Also, the activation of peripheral CD4+ T cells by CNS antigens leads to their extravasation into the CNS causing damages that exacerbates the disease. This could be accompanied by dysregulation of T regulatory cells and other cell types functions. Experimental autoimmune encephalomyelitis (EAE) is a mouse model used to study the pathophysiology of MS disease. In this review, we highlight the roles of innate and adaptive immune players in the pathogenesis of MS and EAE.

Djeya1 (RKLAFRYRRIKELYNSYR), is a very effective cell penetrating peptide (CPP) which mimics the α5 helix of the highly conserved Eya domain (ED) of eyes absent (Eya) proteins. The objective of this study was to bioengineer analogues of Djeya1 that, following effective translocation into planarian tissues, would reduce the ability of neoblasts (totipotent stem cells) and their progeny to regenerate the anterior pole in decapitated S. mediterranea. As a strategy to increase the propensity for helix formation, molecular bioengineering of Djeya1 was achieved by the mono-substitution of the helicogenic aminoisobutyric acid (Aib) at three species variable sites: 10,13,16. CD analyses indicted that Djeya1 is highly helical and that Aib-substitution had little influence on secondary structure. Aib-substituted Djeya1 analogues are highly efficient CPPs, devoid of influence upon cell viability or proliferation. All three peptides increase the migration of PC-3 cells which express high concentrations of Eya. Two peptides, [Aib13]Djeya1 and [Aib16]Djeya1, are bioportides which delay planarian head regeneration. As neoblast are the only cell population capable of division in planaria, these data indicate that bioportide technologies could be utilised to directly manipulate other stem cells in situ, thus negating any requirement for genetic manipulation.

Bacterial conjugation, also referred to as bacterial sex, is a major horizontal gene transfer mechanism where the DNA is transferred from a donor to a recipient bacterium by direct contact. Conjugation is universally conserved among bacteria and occurs in a wide range of environments (soil, plant surfaces, water, sewage, biofilms and host-associated bacterial communities). Within these habitats, conjugation drives the rapid evolution and adaptation of bacterial strains by mediating the propagation of various metabolic properties, including symbiotic life-style, virulence, biofilm formation, or resistance to heavy metals and, most importantly, resistance to antibiotics. These properties make of conjugation a fundamentally important process at the center of extensive study. Here, we review the key steps of conjugation by following the life-cycle of the F plasmid during transfer from the donor to the recipient cell. We also discuss our current knowledge of the extent and impact of conjugation within an environmentally and clinically relevant bacterial habitat, bacterial biofilms.

Universities, like cities, have embraced novel technologies and data-based solutions to improve their campuses with ‘smart’ becoming a welcomed concept. Campuses in many ways are small-scale cities. They increasingly seek to address similar challenges and to deliver improved experiences to their users. How can data be used in making this vision a reality? What can we learn from smart campuses that can be scale up to smart cities? A short research study was conducted over a three-month period at a public university in the United Kingdom employing stakeholder interviews and user surveys, aiming at gaining insight into these questions. Based on the study, the authors suggest that making data publicly available could bring many benefits to different groups of stakeholders and campus users. These benefits come with risks and challenges such as data privacy and protection and infrastructure hurdles. However, if these challenges can be overcome, open data could contribute significantly to improving campuses and user experiences, and potentially set an example for smart cities.

Identification of recurrent driver mutations in genes encoding tyrosine kinases has resulted in the development of molecularly targeted strategies designed to improve the outcomes for patients diagnosed with acute myeloid leukemia (AML). The receptor tyrosine kinase FLT3, is the most commonly mutated gene in AML, with internal tandem duplications within the juxtamembrane domain (FLT3-ITD) or missense mutations in the tyrosine kinase domain (FLT3-TKD), present in 30%-35% of AML patients at diagnosis. An established driver mutation and marker of poor prognosis, the FLT3 tyrosine kinase has emerged as an attractive therapeutic target, and thus has encouraged the development of FLT3 tyrosine kinase inhibitors (TKIs). However, the therapeutic benefit of FLT3 inhibition, particularly as monotherapy, frequently results in the development of treatment resistance and disease relapse. Commonly, FLT3 inhibitor resistance is induced by the emergence of secondary lesions in the FLT3 gene, particularly in the second tyrosine kinase domain at residue Asp835 (D835) to form a ‘dual mutation’ (ITD-D835). Individual FLT3-ITD and FLT3-TKD mutations influence independent signaling cascades however, currently little is known which divergent signaling pathways are controlled by each of these FLT3 specific mutations, particularly in the context of patients harboring dual ITD-D835 mutations. This review provides a comprehensive analysis of the known discrete and cooperative signaling pathways regulated by each of the FLT3 specific mutations, as well as the therapeutic approaches that hold the most promise for development of more durable and personalized therapeutic approaches targeting mutant FLT3, to improve the treatment of AML.

Regeneration of peripheral nerves depends on the ability of axons to navigate through an altered extracellular environment. It has been suggested that Schwann cells facilitate this process through their secretion of neuropeptides and proteases. Using the RT4-D6P2T Schwann cell line (RT4), we have previously shown that RT4 cultures endogenously express the neuropeptide PACAP, and respond to exogenous stimulation by inducing the expression of tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) through PAC1 receptor activation. In this study, based on recent findings showing that doxycycline and minocycline act as positive allosteric modulators (PAMs) of the PAC1 receptor, we tested if treatment with these tetracyclines could induce the expression and activity of tPA and uPA in RT4 cells. Using ELISA and zymographic analyses, we demonstrate that doxycycline and minocycline reliably induce the secretion and activity of both tPA and uPA, which is paralleled by an increased expression levels, as shown by immunocytochemistry and Western blots. These actions were mediated, at least in part, by the PAC1 receptor, as PACAP6-38 mitigated tetracycline-induced expression and activity of tPA and uPA. We conclude that doxycycline and minocycline can act as PAMs of the PAC1 receptor to promote proteolytic activity in RT4 cells.

(1) Background: The incidence of vancomycin-induced neutropenia in hospitalized patients is estimated to be around 2 to 8 percent [1,2]. Data surrounding vancomycin-induced neutropenia is limited as it is based on a small number of observational case reports. Additionally, it is difficult to provide generalized conclusions since patient characteristics and indications for treatment vary between reports. (2) Case Reports: We present two cases of vancomycin-induced neutropenia that occurred at our facility; a 50-year-old male who developed neutropenia after treatment with vancomycin for a gluteal abscess and a 51-year-old female who developed neutropenia after treatment with vancomycin for lumbar osteomyelitis. In both cases, neutropenia resolved within 2 days of discontinuation of vancomycin. (3) Conclusion: The risk of developing neutropenia increases with age, prolonged drug exposure, decreased renal clearance, and in those of female sex. Treatment involves discontinuation of vancomycin with or without administration of granulocyte colony-stimulating factor (G-CSF). Additional studies are needed to better understand the true incidence of this adverse drug reaction and to identify risk factors that may predispose patients to vancomycin-induced neutropenia.

Seafood, especially from the ocean, is now seen as a greener and more sustainable source of protein causing an increase in its demand. This has also led to people making choices towards seafood as a replacement of carbon intensive protein sources. As a result, the demand for seafood is growing, and the Aquaculture industry is required to increase their produce while keeping the produce safe and sustainable. There are many challenges faced by the aquaculture industry in meeting these increased demands. One such challenge is the presence of harmful algal blooms (HAB) in the ocean which can have a major impact on aquatic life. In this paper we look at the impact of this challenge on aquaculture and the mitigating strategies. We will focus on Abagold Limited, a land-based marine aquaculture business that specializes in large scale production of abalone (Haliotis midae) based in Hermanus, South Africa. HABs are considered a threat to commercial scale abalone farming along the South-African coastline and requires continuous monitoring. The most recent HAB was in February-April 2019, the area experienced a severe red-tide event with blooms of predominantly Lingulodinium polyedrum. We present some of the mitigation strategies employing digital technologies for future proofing the industry.

There is increasing evidence that some adult mitral valve pathologies may have developmental origins involving errors in cell signaling and protein deposition during valvulogenesis. While early and late gestational stages are well-documented in zebrafish and small mammalian models, longitudinal studies in large mammals with a similar gestational period to humans are lacking. Further, the mechanism of chordae tendineae formation and multiplication remains unclear. This current study presents a comprehensive examination of mitral anterior leaflet and chordae tendineae development in a bovine model (with a gestational period of 9 months). Remarkably distinct from small mammals, bovine development displayed early branched chordae, with increasing attachments only until birth, while the anterior leaflet grew both during gestation and postnatally. Chordae also exhibited accelerated collagen deposition, maturation, and crimp development during gestation. These findings suggest that the bovine anterior leaflet and chordae tendineae possess unique compartmentalized processes of development despite being a continuous collagenous structure.

To meet the calls of the International Labor Organization and National Institutes of Occupational Safety and Health, this paper discusses how to build Occupational, Health, Safety (OSH), and Well-Being competence by expanding education to non-traditional undergraduate disciplines. The authors provide (1) theoretical background on why this would benefit society as a whole, (2) learning theory strategies for teaching OHS and Well-being outside of traditional majors, (3) case studies of how this can occur in undergraduate classes and (4) opportunities and challenges for the future.

Important current limitations of the implementation of Evidence-Based Practice (EBP) in the rehabilitation field are related to the validation process of new technologies and interventions. Indeed, most of the strict guidelines that have been developed for the validation of new drugs (i.e., double or triple blinded, strict control of the doses and intensity) cannot – or only partially – be applied in rehabilitation. Well powered high quality randomized controlled trials are more difficult to organize in rehabilitation (e.g., longer duration of the intervention in rehabilitation, more difficult to standardize the intervention compared to drugs’ validation studies, limited funding’s since not sponsorized by big pharma companies), which reduces the possibility of conducting systematic reviews and meta-analyses, as currently high level of evidence is sparse. The current limitations of EBP in rehabilitation are presented in this paper and innovative solutions are suggested such as: technology-supported rehabilitation systems, continuous assessment, pragmatic trials, rehabilitation treatment specification systems, and advanced statistical methods, to tackle the limitations to increase the quality of the research in rehabilitation. The development and implementation of new technologies should increase the quality of research and the level of evidence supporting rehabilitation provided some adaptation in our research methodology.

: Julia Creek dunnarts are an endangered species of carnivorous marsupials and the focus of multiple conservation strategies involving significant resources such as captive breeding programs. Despite the relevance for conservation, no study to date has focused on evaluating geriatric diseases in dunnarts. This study describes the pathology findings in a group of one wild and 35 captive-born, mostly geriatric Julia Creek dunnarts that failed to produce offspring over multiple breeding periods. A total of 20 females and 16 males were submitted for a postmortem examination, with ages ranging from 9-42 and 12-42 months for females and males, respectively. Of these, 10 had unremarkable findings. The most common condition in females was cystic glandular hyperplasia (n=8), typical of hormonal dysregulation profiles in senescence, particularly hyperestrogenism. Rarely, cutaneous disease represented by unidentified dermal round cell infiltrates was observed in females (n=2). Primary reproductive hormonal dysregulation was also suspected in males diagnosed with testicular degeneration, aspermatogenesis and/or atrophy (n=3). Cutaneous round cell infiltrates, possibly compatible with epitheliotropic lymphomas were seen in males (n=3), and 2/3 affected males also had concurrent testicular degeneration or atrophy, indicating male sex could be a predictor for lymphoid neoplasia in aged dunnarts especially in individuals with concurrent testosterone-luteinizing hormone dysregulation as it occurs in gonadectomized animals. The role of an underlying viral etiology is also explored. This study is the first to describe major spontaneous diseases in endangered aged Julia Creek dunnarts, providing an important understanding of senescence and geriatric diseases within a conservation context.

Despite their prevalence in almost all publicly orientated conservation settings, sign design receives limited attention in the research literature. We used a remote eye-tracking device to test how visitors read educational signs, maps, and species signage. Three designs, plus a plain-text control sign, were tested for each sign type. Sign content was based on Brackenhurst Botanic Garden, Kenya and included four different information texts (156-256 words long) and a species information text (64 words long). Four presentations of extinction threat-status were also tested as were depictions of trail routes on maps. Data were collected from 51 participants at six cultural venues across Nottingham, UK. Signs positioned centre-left of an exhibit were read first. Information on the left-hand side of signs was read first and dwelled upon the longest. Signs with a single large image and a single block of text were generally preferred, and images were most frequently recalled. Extinction threat-status was most frequently viewed and best recalled from green-red thermometer diagrams and least from the IUCN red-list diagram. Map routes were clearest when presented as coloured solid lines. This study indicates the potential benefit of eye-tracking research for measuring sign use and assisting in sign design.

PTB7-Th is an important donor copolymer used in construction of many organic devices and other industrial applications. In this work, we investigate the structure and energetics of PTB7-Th. We employ density functional theory (DFT) (B3LYP), dispersion corrected DFT (B3LYP-D3) and long-range corrected DFT (CAM-B3LYP, LC-BLYP, and ωB97xD) to analyze the conformational structures and their corresponding energies to determine the lowest energy state of PTB7-Th. The role of the alkane side chains is carefully investigated. Our findings indicate that, when branched ethylhexyl side chains are present, the lowest energy structure of PTB7-Th has fluorine in the same plane and the same side as the double bonded oxygen in the TT-CF part of the monomer and S-C-C-S dihedral angles along the chain backbone are cis-like having values in the range of 20-30 degrees in most cases. Without these side chains the polymer, not unexpectedly, has many near conformational degeneracies.

The model proposed in this study was based on the assumption that the biomass attached to the anode served as biocatalysts for MFC exoelectrogenesis, and this catalytic effect was quantified by the exchange current density of anode. By modifying the Freter model and combining it with the Butler-Volmer equation, this model could adequately describe the processes of electricity generation, substrate utilization, and the suspended and attached biomass concentrations, at both batch and continuous operating modes. MFC performance is affected by the operating variables such as initial substrate concentration, external resistor, influent substrate concentration, and dilution rate, and these variables were revealed to have complex interactions by data simulation. The external power generation and energy efficiency were considered as indices for MFC performance. The simulated results explained that an intermediate initial substrate concentration (about 100 mg/L under this reactor configuration) needed to be chosen to achieve maximum overall energy efficiency from substrate in the batch mode. An external resistor with the value about that of the internal resistance boosted the power generation, and a resistor with several times of that of the internal resistance achieved better overall energy efficiency. At continuous mode, dilution rate significantly impacted the steady-state substrate concentration level (thus substrate removal efficiency and rate), and attached biomass could be fully developed when the influent substrate concentration was equal to or higher than 100 mg/L at any dilution rate of the tested range. Overall, this relatively simple model provided a convenient way for evaluating and optimizing the performance of MFC reactors by regulating operating parameters.

Diet plays a pivotal role in the overall health of an individual. Not only does it help carry out and regulate certain physiological functions, but it also can determine the composition of the gut microbiome. While the relative number of microorganisms that make up the gut microbiome vary between individuals and can be dependent on different environmental factors, there is evidence to suggest that composition of the microbiome can correlate with overall health or disease. When the GI microbiome is disturbed or suddenly changes it results in microbiome dysbiosis, a condition that correlates with the presence of certain diseases. Diseases linked to microbiome dysbiosis range from metabolic disorders, inflammatory bowel diseases to disorders of the brain. Many of these diseases are linked to the connection between the brain and the gut, known as the brain-gut axis. This bidirectional communication is important to maintain normal intestinal function, but is also responsible for the GI response to emotions as well as the emotional response to GI disturbances. By exploiting the interaction between microbiome health and nutrition, diet can be used to alleviate disease symptoms, protect against the development of certain conditions, and better maintain overall health. This review will examine the effects of nutrition on the microbiome, diseases linked to disruption of the normal microbiome, and the way that altering the diet can mitigate symptoms or prevent disease.

Following traumatic brain injury (TBI), secondary brain damage due to chronic inflammation is the most predominant cause of the delayed onset of mood and memory disorders. Currently no therapeutic approach is available to effectively mitigate secondary brain injury after TBI. One reason is the blood-brain barrier (BBB), which prevents passage of most therapeutic agents into the brain. Peptides have been among the leading candidates for CNS therapy due to their low immunogenicity and toxicity, bioavailability, and ease of modification. In this study, we demonstrated that non-invasive intranasal administration of KAFAK, a cell penetrating anti-inflammatory peptide, traversed the BBB in a murine model of diffuse, moderate TBI. Notably, KAFAK treatment reduced the production of pro-inflammatory cytokines that contribute to secondary injury. Furthermore, behavioral tests showed improved or restored neurological, memory, and locomotor performance in KAFAK-treated mice. This study demonstrates KAFAK's ability to cross the blood-brain barrier, to lower pro-inflammatory cytokine levels in vivo, and to restore function after a moderate TBI.

Intuitionistic fuzzy set, which can be represented using the triangular intuitionistic fuzzy number (TIFN), is a more generalized platform for expressing imprecise, incomplete and inconsistent information when solving multi-criteria decision-making problems, as well as for reflecting the evaluation information exactly in different dimensions. In this paper, the TIFN has been applied for solving some multi-criteria decision-making problems by developing a new triangular intuitionistic fuzzy geometric aggregation operator, that is the generalized triangular intuitionistic fuzzy ordered weighted geometric averaging (GTIFOWGA) operator, and defining some triangular intuitionistic fuzzy geometric aggregation operators including the triangular intuitionistic fuzzy weighted geometric averaging (TIFWGA) operator, the ordered weighted geometric averaging (TIFOWGA) operator and the hybrid geometric averaging (TIFHWGA) operator. Based on these operators, a new approach for solving multicriteria decision-making problems when the weight information is fixed has been proposed. Finally, the proposed method has been compared with some similar existing computational approaches by virtue of a numerical example to verify its feasibility and rationality.

Background and Objectives: Gastric cancer (GC) is one of the most commonly diagnosed cancer and the fourth cause of cancer death worldwide. Personalised treatment improves GC outcomes. A molecular classification is needed to choose the appropriate therapy. A classification that uses on-slide biomarkers and formalin-fixed and paraffin-embedded (FFPE) tissue is preferable to comprehensive genomic analysis. In 2016, Setia et al. proposed an on-slide classification, however this is not in widespread use. We propose a modification of this classification that has six subgroups: GC associated with Epstein-Barr virus (GC EBV+), GC with mismatch repair deficiency (GC dMMR), GC with epithelial-mesenchymal transformation (GC EMT), GC with functional loss of p53 due to mutation (GC p53m), CG with intact p53 (GC p53wt) and GC not otherwise specified (GC NOS). This classification also has provision for biomarkers for current or emerging targeted therapies (Her2, PD-L1 and Claudin18.2). Here we assess the implementation and feasibility of this inclusive working classification. Materials and Methods: We constructed a tissue microarray library from a cohort of 79 resection cases from FFPE tissue archives. We used a restricted panel of on-slide markers (EBER, MMR, E-cadherin, beta-catenin and p53), defined their interpretation algorithms, and assigned each case to a specific molecular subtype. Results: GC EBV(+) cases were 6%, GC dMMR cases were 20%, GC EMT cases were 14%, GC p53m cases were 23%, GC p53wt cases were 29% and GC NOS cases were 8%. Conclusions: This working classification uses markers that are widely available in Histopathology and are easy to interpret. A diagnostic subgroup is obtained for 92% of the cases. The proportion of cases in each subgroup is in keeping with other published series. Widescale implementation appears feasible. A study using endoscopic biopsies is warranted.

Behavioural disorders in dogs are common and have severe welfare consequences for dogs. This study aimed to assess the factors that are significant and predictive of behaviour problems in dogs using the Animal Welfare Assessment Grid (AWAG) to further understand what factors influence their welfare. 177 AWAG assessments were undertaken across 129 dogs that clinicians deemed to have a behavioural disorder. Wilcoxon-rank sum tests were used to assess the difference in scores between dogs with behaviour disorders and a cohort of healthy dogs (n=117). This analysis showed that all physical factors besides body condition, all procedural factors besides procedure pain, and all psychological, and environmental factors were significantly different between healthy dogs and dogs with behaviour disorders. Spearman Rank Correlation Coefficient (RS) revealed several significant strong positive correlations including the procedural impact on the dog’s daily routine with aggression towards unfamiliar people and procedure pain, as well as other correlations between the dog’s behaviour during assessment with the frequency at which they encounter fears and anxieties, clinical assessment and procedure pain, and reaction to stressors and social interactions. These findings highlight the interdependent nature of the various influences of welfare. Logistic regression analysis identified that aggression towards the caregiver, fears and anxieties frequency, and choice, control, and predictability were all significant predictors of behaviour disorders. The findings have important implications for veterinary, behaviour, and animal welfare professionals as any changes across these factors may indicate poor welfare linked to emotional disorders in dogs.

Mental health issues can have significant impacts on individuals and communities and hence on social sustainability. There are several challenges facing mental health treatment, however, more important is to remove the root causes of mental illnesses because doing so can help prevent mental health problems from occurring or recurring. This requires a holistic approach to understanding mental health issues that are missing from the existing research. Mental health should be understood in the context of social and environmental factors. More research and awareness are needed, as well as interventions to address root causes. The effectiveness and risks of medications should also be studied. This paper proposes a big data and machine learning-based approach for the automatic discovery of parameters related to mental health from Twitter data. The parameters are discovered from three different perspectives, Drugs & Treatments, Causes & Effects, and Drug Abuse. We used Twitter to gather 1,048,575 tweets in Arabic about psychological health in Saudi Arabia. We built a big data machine learning software tool for this work. A total of 52 parameters were discovered for all three perspectives. We defined 6 macro-parameters (Diseases & Disorders, Individual Factors, Social & Economic Factors, Treatment Options, Treatment Limitations, and Drug Abuse) to aggregate related parameters. We provide a comprehensive account of mental health, causes, medicines and treatments, mental health and drug effects, and drug abuse, as seen on Twitter, discussed by the public and health professionals. Moreover, we identify their associations with different drugs. The work will open new directions for social media-based identification of drug use and abuse for mental health, as well as other micro and macro factors related to mental health. The methodology can be extended to other diseases and provides a potential for discovering evidence for forensics toxicology from social and digital media.

Quaking aspen (Populus tremuloides Michx.) is an important deciduous species in western U.S. forests. Existing maps of aspen distribution are based on Landsat imagery and often miss small stands (&lt;0.09 ha or 30 m²), which rapidly regrow when managed or following disturbance. In this study, we present methods for deriving a new regional map of aspen forests using one year of Sentinel-1 (S1) and Sentinel-2 (S2) imagery in Google Earth Engine. We assessed the annual phenology of aspen in the Southern Rockies and leveraged the frequent temporal resolution of S1 and S2 to create ecologically relevant seasonal composites. Additionally, we derived spectral indices and radar textural features targeting the canopy structure, moisture, and chlorophyll content. Using spatial block cross-validation and Random Forests, we assessed the accuracy of different scenarios and selected the best performing set of features for classification. Comparisons were then made with existing landcover products across the study region. The resulting map improves on existing landcover products in both accuracy (average F1-score = 93.1%) and detection of smaller forest patches. These methods enable accurate mapping at spatial and temporal scales relevant to forest management for one of the most widely distributed tree species in North America.

Stingless bee beekeeping provides new opportunities to improve the incomes of many households in Malaysia through the sale of honey and other bee products. While Heterotrigona itama is one of the most commonly cultured species of stingless bees, its behavior is not very well understood. Hence, we conducted this study to investigate the behavior of H. itama in exploiting food sources by ascertaining the nectar sugar concentration preferred by the bee. We also aimed to determine the preferred distance of food source from the bee hive. Our results suggest that H. itama prefers high sugar concentrations of 35% and above, and they would fly up to 7 m from the hive to collect food. We discuss how nectar concentration and food distance influence the number of bees exploiting food sources and the overall foraging pattern of H. itama.

The extracellular matrix (ECM) provides structural support for tissues and regulatory signals for resident cells. ECM requires a careful balance between protein accumulation and degradation for homeostasis. Disruption of this balance can lead to pathological processes such as fibrosis in organs across the body. Post-translational crosslinking modifications to ECM proteins such as collagens alter ECM structure and function. Dysregulation of crosslinking enzymes as well as changes in crosslinking composition are prevalent in fibrosis. Because of the crucial roles that ECM crosslinking pathways play in disease, the enzymes that govern crosslinking events are being explored as therapeutic targets for fibrosis. Here we review in-depth the molecular mechanisms underlying ECM crosslinking, how ECM crosslinking contributes to fibrosis, and therapeutic strategies being explored to target ECM crosslinking in fibrosis to restore normal tissue structure and function.

The automatic classification of bird sounds is an ongoing research topic and several results have been reported for the classification of selected bird species. In this contribution we use an artificial neural network fed with pre-computed sound features to study the robustness of bird sound classification. We investigate in detail if and how classification results are dependent on the number of species and the selection of species in the subsets presented to the classifier. In more detail, a bag-of-birds approach is employed to randomly create balanced subsets of sounds from different species for repeated classification runs. The number of species present in each subset is varied between 10 and 300, randomly drawing sounds of species from a dataset of 659 bird species taken from Xeno-Canto database. We observe that the shallow artificial neural network trained on pre-computed sound features is able to classify the bird sounds relatively well. The classification performance is evaluated using several common measures such as precision, recall, accuracy, mean average precision and area under the receiver operator characteristics curve. All of these measures indicate a decrease in classification success as the number of species present in the subsets is increased. We analyze this dependence in detail and compare the computed results to an analytic explanation assuming dependencies for an idealized perfect classifier. Moreover, we observe that the classification performance depends on the individual composition of the subset and varies across 20 randomly drawn subsets.

Sorting nexins (SNXs) are a highly conserved membrane-associated protein family that plays a role in regulating protein homeostasis. This family of proteins is unified by their characteristic phox (PX) phosphoinositides binding domain. Along with binding to membranes, this family of SNXs also comprises a diverse array of protein-protein interaction motifs that are required for cellular sorting and protein trafficking. SNXs play a role in maintaining the integrity of the proteome which is essential for regulating multiple fundamental processes such as cell cycle progression, transcription, metabolism, and stress response. To tightly regulate these processes proteins must be expressed and degraded in the correct location and at the correct time. The cell employs several proteolysis mechanisms to ensure that proteins are selectively degraded at the appropriate spatiotemporal conditions. SNXs play a role in ubiquitin-mediated protein homeostasis at multiple levels including cargo localization, recycling, degradation, and function. In this review, we will discuss the role of SNXs in three different protein homeostasis systems: endocytosis lysosomal, the ubiquitin-proteasomal, and the autophagy-lysosomal system. The highly conserved nature of this protein family by beginning with the early research on SNXs and protein trafficking in yeast and lead into their important roles in mammalian systems. Underlying the importance of SNXs in protein homeostasis, genetic defects in SNXs have been linked with a variety of human diseases such as cancer, cardiovascular disease, neurogenerative disease, and viral infections.

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

Research rarely explores LGBTQ+ youth bullying in the context of culture-specific outcomes (e.g., LGBTQ+ identity development) and what can mitigate the impact of peer stressors. This study used a concurrent mixed methods design to explore how experiences of peer victimization predicted LGBTQ+ youth’s identity development (i.e., stigma sensitivity, concealment motivation, and difficult process) and whether social support and outness served as protective, moderating factors. The mixed-methods approach provides a culture-specific context via qualitative inquiry to inform whether the quantitative findings align with how youth qualitatively discuss their experience of bullying, negative outcomes, and social support. Our sample consisted of 349 LGBTQ+ youth 14-17 years old who completed a survey (quantitative sample), and a subset of 39 LGBTQ+ youth who completed a semi-structured interview (qualitative sample). Our quantitative findings indicated that greater overall peer victimization was positively related to LGBIS-revised subscales of stigma sensitivity, concealment motivation, and difficult process, where both outness and social support moderated such relations. Qualitatively, victimized youth also reported stigma sensitivity and concealment motivation, while also endorsing how being out and having a support system played a role in their experience of being victimized. These qualitative findings align with our quantitative findings that classmate support mitigated the effects of peer victimization on difficulty of coming out. Implications for practitioners and researchers are provided.

Most shear tests are performed as standard three- or four-point bending tests, i.e., on one-way simply supported specimens subjected to concentrated loads. The major disadvantage is that these conditions usually do not correspond to the support and load condition of real structures. Structural members such as beams or slabs, are often multi-span components and subjected to distributed loads. As a consequence, the complex shear behavior, including crack kinematics, shear transfer mechanisms, and shear capacity, is studied almost only simply supported members with concentrated load. Positive impacts on the shear behavior resulting from continuous systems and distributed loads are thus neglected in the derivation of calculation models and in the development of design specifications. To incorporate the effect of continuous members and distributed loading conditions, more experimental investigations are necessary. Therefore, a total of 16 bending shear tests on CFRP reinforced concrete members without shear reinforcement were carried out. The tests specimens were tested as simply supported beams or as simply supported beams with loaded cantilever to simulate the continuous system with concentrated and distributed loads. Furthermore, the shear slenderness was varied by using different span lengths and degrees of restraint in the systems with intermediate support. All test specimens were made of high-strength concrete and were reinforced with a multilayer grid-like CFRP reinforcement in longitudinal direction. There was no shear reinforcement installed in the investigated shear span. This paper focuses the influence of the support conditions and load arrangements on crack development as well as on shear strength.

Diseases of the lung account for more than 5 million deaths worldwide and are a burden to healthcare. Improving clinical outcomes including mortality and quality of life involves a holistic understanding the etiopathogenesis, which can be provided by multi-omics integration of lung data. An enhanced understanding of large comprehensive datasets provides opportunities to mine those datasets for features that contribute to prevention and amelioration of disease. In this review, we evaluate lung disease models including animal models, organoids and single cell lines as mechanisms to study multiomics in lung health and disease. We provide examples of lung diseases where multi-omics investigations have provided a deeper insight into pathogenesis that has resulted in improved preventive and therapeutic interventions.

SARS-CoV-2 infection can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. However, strategies to predict the course of SARS-CoV-2 infection in CVD patients at the time of hospital admission are still missing. Here, we investigated whether this prediction is achievable by prospectively analysing the blood immunophenotype of 94 participants, including 20 uninfected and 37 acutely SARS-CoV-2-infected CVD patients and 37 healthy donors, using a 36-colour spectral flow cytometry panel. Unsupervised data analysis revealed little differences between healthy donors and CVD patients, whereas the distribution of the cell populations changed dramatically in SARS-CoV-2-infected CVD patients. The latter had more mature NK cells, activated monocyte subsets, central memory CD4+ T cells, and plasmablasts but fewer dendritic cells, CD16+ monocytes, innate lymphoid cells, and CD8+ T cell subsets. Moreover, we identified an immune signature characterised by mucosal-associated invariant T (MAIT) cells, intermediate effector CD8+ T cells, and natural killer T (NKT) cells that is predictive for CVD patients with a severe course of COVID-19. Thus, intensified immunophenotype analyses can help identify patients at risk of severe COVID-19 at hospital admission, improving clinical outcomes through specific treatment.

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

Tyrosine Kinase Inhibitors work by blocking the tyrosine kinases responsible of the dysregulation of intracellular signalling pathways in tumour cells. This study looked at the impact of age and sex on the levels of imatinib, dasatinib, nilotinib, and ponatinib in plasma and cerebrospinal fluid samples of patients with chronic myeloid leukaemia. Imatinib and dasatinib were used to treat the majority of the enrolled patient and most of them were paediatrics. The 82.4% of patients were men; however, sex-related differences in drugs pharmacokinetics were not found. Age and imatinib plasma concentration were found to be inversely correlated: as patients ages increased, drug levels decreased. The dasatinib concentrations in plasma were found to be substantially lower than those found in cerebrospinal fluid, particularly in paediatrics. Analysing the obtained data, we can state that Therapeutic Drug Monitoring is a useful method for adjusting a patient treatment schedule depending on drug concentrations in biological fluids. The use of Therapeutic Drug Monitoring in conjunction with Tyrosine Kinase Inhibitors for the treatment of chronic myeloid leukaemia is supported by a number of sources of evidence. As a result, as the research develops, Tyrosine Kinase Inhibitors Therapeutic Drug Monitoring classification needs to be refined in terms of factors like sexes and ages.

Immune checkpoint blockade (ICB) has revolutionized the prognosis of several advanced-stage solid tumors. However, its success has been far more limited in hematological malignancies and is mostly restricted to classical Hodgkin lymphoma (cHL) and primary mediastinal B cell lymphoma (PMBCL). In patients with non-Hodgkin lymphoma (NHL), response to PD-1/PD-L1 ICB monotherapy has been relatively limited, although some subtypes are more sensitive than others. Numerous predictive biomarkers have been investigated in solid malignancies, such as PD-L1 expression, tumor mutational burden (TMB) and microsatellite instability (MSI), among others. This case-illustrated review aims to appraise the current knowledge on PD-1/PD-L1 ICB efficacy in lymphoid malignancies, when used either as monotherapy or combined with other agents, and describes potential biomarkers of response in this specific setting.

Plant breeding primarily focuses on improving conventional agronomic traits, e.g. yield, quality, and resistance to biotic and abiotic stress; however, genetic improvement methods are being rapidly enhanced through genomics and phenomics. In the Genomics-Phenomics-Agronomics (GPA) paradigm, diverse research approaches have been conducted to bridge any two of these elements, and recently, all of them together. This review first highlights the progress to link i) genomics to agronomics; ii) genomics to phenomics; and iii) phenomics to agronomics. Secondly, the GPA domain is dissected into different layers, each addressing the three elements simultaneously. These dissected layers include genetic dissection through gene mapping using genome-wide association studies and genomic selection using Best Linear Unbiased Prediction, Bayesian approaches, and machine learning. The objective of the review is to help readers to grasp the core developments among the exponentially growing literature in each of these fields. Through this review, the connections among the three elements of the GPA paradigm are coherently integrated toward the prospect of sustainable development of agronomic traits through both genomics and phenomics.

Understanding surfactant self-assembly in deep eutectic solvents (DES) is important to their potential use in industrial formulations. We have recently reported the formation of a fracto-eutectogel comprising SDS fractal aggregates at a concentration as low as 1.6 wt% in glyceline (a DES comprising glycerol and choline chloride) at room temperature. The building units of the fractals consisted of multilayers of self-assembled SDS lamellae arranged in a dendritic pattern. Here we report that this fractal phase transitions into a fluid phase above a critical gelation temperature, TCG ~ 45 oC, evident from polarized light microscopy (PLM) observations. Small-angle neutron scattering (SANS) reveals that this phase transition is underpinned by the nanoscopic morphological transformation of the SDS lamellae into cylindrical micelles at T &gt; TGC. Fitting SANS profiles confirms that the morphology of the micelles is SDS-concentration (cSDS) dependent at T &gt; TGC: cylindrical at cSDS &gt; 0.6 wt% and spherical at cSDS = 0.6 wt%. At cSDS &lt; 0.6 wt%, only isotropic scattering was observed in the SANS profiles. Such SDS self-assembly behaviors contrast with those we have previously observed in glycerol, which we attribute to the presence of ions (i.e. choline chloride) in glyceline. Our findings have general implications to surfactant self-assembly in DES, solvents that are rich in hydrogen bonding and ions.

This paper presents a hydrodynamic numerical model for a pitching wave energy converter (WEC). The model uses potential wave theory and is based on Cummins' equation, with nonlinear hydrostatic restoring stiffness and excitation forces based on instantaneous body position and water surface elevation. The numerical model can include non-linear forces, like quadratic drag, power-take-off and other forces that may account for unknown viscous effects observed in experiments. The paper discusses the applicability and limitations of the code and presents the cases where assumptions and simplifications can be made. The goal is to conclude on the simplest, yet accurate, version of the model by evaluating its accuracy using experimental data. The case study for validation is Floating Power Plant's (FPP's) WEC [1]. In the full-scale commercial project, FPP's device consists of a semisubmersible platform hosting a wind turbine (5-8MW) and 4 WECs, each one connected to the platform by a rotation shaft. Due to the configuration of the platform, strong interactions occur between the WECs and the structure, as they are very closely spaced. In order to validate a numerical model able to simulate these hydrodynamic interactions, wave basin experiments with a similar but simplified setup were performed.

Background: HIV poses a threat to global health. With effective treatment options available, education and testing strategies are essential in preventing transmission. Text messaging is an effective tool for health promotion and can be used to target higher risk populations. This study reports on the design, delivery and testing of a mobile text messaging SMS intervention for HIV prevention and awareness, aimed at adults in the construction industry and delivered during the COVID-19 pandemic. Method: Participants were recruited at Test@Work workplace health promotion events (21 sites, n=464 employees), including health checks with HIV testing. Message development was based on a participatory design and included a focus group (n=9) and message fidelity testing (n=291) with assessment of intervention uptake, reach, acceptability, and engagement. Barriers to HIV testing were identified and mapped to the COM-B behavioural model. 23 one-way push SMS messages (19 included short web links) were generated and fidelity tested, then sent via automated SMS to two employee cohorts over a 10-week period during the COVID-19 pandemic. Engagement metrics measured were; opt-outs, SMS delivered/read, number of clicks per web link, and four two-way pull messages exploring repeat HIV testing, learning new information, perceived usefulness and behaviour change. Results: 291 people participated (68.3% of eligible attendees). A total of 7,726 messages were sent between March and June 2020, with 91.6% successfully delivered (100% read). 12.4% of participants opted out over 10 weeks. Of delivered messages, links were clicked an average of 14.4%, max 24.1% for HIV related links. The number of clicks on web links declined over time (r= -6.24, p=0.01). Response rate for two-way pull messages was 13.7% of participants. Since the workplace HIV test offer at recruitment, 21.6% reported having taken a further HIV test. Qualitative replies indicated behavioural influence of messaging on exercise, lifestyle behaviours and intention to HIV test. Conclusion: SMS messaging for HIV prevention and awareness is acceptable to adults in the construction industry, has high uptake, low attrition and good engagement with message content, when delivered during a global pandemic. Data collection methods may need refinement for audience and effect of COVID-19 on results is yet to be understood.

The COVID-19 pandemic has had devastating consequences for health, social, and economic domains, but what has received far less focus is the effect on people’s relationship to vital ecological supports, including access to greenspace. We assessed patterns of greenspace use in relation to individual and environmental factors and their relationship with experiencing psychological symptoms under the pandemic. We conducted an online survey recruiting participants from social media for adults in Korea for September–December 2020. The survey collected data on demographics, patterns of using greenspace during the pandemic, and major depression (MD) and generalized anxiety disorder (GAD) symptoms. The Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder 2-item (GAD-2) were applied to identify probable cases of MD and GAD. A logistic regression model assessed the association decreased visits to greenspace after the outbreak compared to 2019 and probable MD and GAD. Among the 322 survey participants, prevalence of probable MD and GAD were 19.3% and 14.9%, respectively. High rates of probable MD (23.3%) and GAD (19.4%) were found among persons currently having job-related and financial issues. Of the total participants, 64.9% reported decreased visits to greenspace after the COVID-19 outbreak. Persons with decreased visits to greenspace had 2.06 higher odds (95% CI: 0.91, 4.67) of probable MD at the time of the survey than persons whose visits to greenspace increased or did not change. Findings suggest that barriers to greenspace use could deprive people of mental health benefits and affect mental health during pandemic; an alternative explanation is that those experiencing poor mental health may be less likely to visit greenspaces during pandemic. This implies the need of adequate interventions on greenspace uses under an outbreak especially focusing on how low-income populations may be more adversely affected by a pandemic and its policy responses.

Objective: To explore motivation to exercise, support, and self-management needs among people with Parkinson’s (PwP), family-members and physiotherapists. Methods: Purposeful and maximum difference sampling methods (age, sex, geographical setting, and disease severity) were employed. PwP and family-members were recruited through physiotherapy services and local support groups. Semi-structured interviews with 12 PwP, focus groups with four family-members, and five physiotherapists were conducted. Interview guides were informed by patient-public input, and a recent systematic review. Interviews were recorded, transcribed, and analysed using thematic analysis. Results: Four common themes emerged: 1) The value of an intrinsic connection with exercise: but there are challenges. A greater connection to exercise led to long-term compliance. 2) Tailoring exercise is essential. Preferred exercises and environments were mixed, with differences emerging between sexes. 3) Physiotherapists’ aim to only maintain physical function led to frustration. Limited self-management opportunities, stigma and dehumanisation were discussed. 4) Non-motor symptoms, stigma, fear, and determination. Apathy, pain, and low mood were discussed. Conclusion: Exercise provided physical, emotional, and social rewards. Supports are necessary; however, challenges arise when PwP’s motivation are mismatched to family-members’ and physiotherapists’ goals. Co-created goals, tailored to their preferences, and exercise plans with supported self-management are recommended.

In 2018, the state of Himachal Pradesh in north India launched an initiative to convert all its farmers to natural farming (NF), an agroecological approach. The aim was to address multiple challenges related to rural livelihoods, high input costs, biodiversity loss, and environmental degradation. This paper is based on a qualitative case study of the state programme to transition farmers to NF. It seeks to understand how its mechanisms support and empower small and marginal women farmers. In addition to identifying mechanisms that facilitate the effective uptake of NF, the case study sought women's views on whether these increased spaces for decision-making and developed capabilities and autonomy. Framed within the vision of reclaiming food sovereignty, various mechanisms such as training in villages, participating in NF groups and networks, visits to model farms and adopting leadership roles offered new pathways for women farmers to gain confidence and capabilities. Women began to participate in spaces that had been culturally and structurally denied to them. This case study illustrates how agroecology efforts with a specific focus on gender have the potential to provide women with creative outlets and a variety of decision-making and income-generating roles, spaces for community learning and knowledge needed for sustainable ecosystems.

Magnetic ceramic nanoparticles system xTm2O3-(1-x)alpha-Fe2O3 (x=0.1 and 0.5) was synthesized by mechanochemical activation starting from hematite and thulium oxide precursors and characterized by transmission Mӧssbauer spectroscopy. The Mӧssbauer spectra were typically analyzed considering 1-3 sextets, corresponding to hematite (with and without thulium doping) and a doublet, representing thulium iron perovskite (thulium orthoferrite). The magnetic hyperfine fields (BHF) and doublet abundance were studied as function of the ball milling time (BMT) for both molar concentrations employed. The results are consistent with the formation of solid solutions in the investigated system. The mixed-oxide nanoparticle system synthesized may have important applications in displays, sensors and photovoltaics, and is paving the way for emerging utilizations related to mechanically flexible electronics.

Metastasis is a critical step in the process of carcinogenesis and a vast majority of cancer related mortalities result from metastat-ic disease that is resistant to current therapies. Cell migration and invasion are the first steps of the metastasis process, which mainly occurs by two important biological mechanisms i.e., cytoskeletal remodelling and Epithelial to Mesenchymal Transition (EMT). Akt (also known as Protein Kinase B) is a central signalling molecule of the PI3K-Akt signalling pathway. Aberrant acti-vation of this pathway has been identified in a wide range of cancers. Several studies have revealed that Akt actively engages with the migratory process in motile cells, including metastatic cancer cells. The downstream signalling mechanism of Akt in cell migration depends upon the tumour type, sites, and intracellular localisation of activated Akt. In this review, we focus on the role of Akt in the regulation of two events that control cell migration and invasion in various cancers including head and neck squamous cell carcinoma (HNSCC) and the status of PI3K-Akt pathway inhibitors in clinical trials in HNSCC.

Since the first confirmed case of COVID-19, information was spreading in large amounts over social media platforms. Information spreading about the COVID-19 pandemic can strongly influence people’s behavior. Therefore, identifying information superspreaders (or influencers) during the COVID-19 pandemic is an im- portant step towards understanding public reactions and information dissemination. In this work, we present an analysis over a large Arabic tweets collected during the COVID-19 pandemic. The presented study con- struct a network from users’ behaviors to identify information superspreaders during the month of March, 2020. We employed both HITS and PageRank algorithms to analyze the influence of information spreading, and compared the ranking of the users. The results show that both HITS and PageRank discovered a similar subset of superspreaders with 40% were found to be verified Twitter accounts.

The underlying molecular basis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is not well understood. Characterized by chronic, unexplained fatigue, a disabling payback following exertion (“post-exertional malaise”) and variably presenting, multi-system symptoms, ME/CFS is a complex disease which demands concerted biomedical investigation from disparate fields of expertise. ME/CFS research and patient treatment have been challenged by the lack of diagnostic biomarkers and finding these is a prominent direction of current work. Despite these challenges, modern research demonstrates a tangible biomedical basis for the disorder across many body systems. This evidence is largely comprised of disturbances to immunological and inflammatory pathways, autonomic and neurologic systems, abnormalities in muscle and mitochondrial function, shifts in metabolism, and gut physiology or gut microbiome disturbances. It is possible that these threads are together entangled as parts of an underlying molecular pathology reflecting a far-reaching homeostatic shift affecting each of these systems. Due to the variability of non-overlapping symptom presentation or precipitating events such as infection or other bodily stresses, the initiation of body-wide pathological cascades with similar outcomes stemming from different causes may be implicated in the condition. Patient stratification to account for this heterogeneity is therefore one important consideration during exploration of potential diagnostic developments.

ABSTRACT:This paper presents arguments for why it is important to include disability in the undergraduate medical curriculum. I, the first author am currently involved with my doctoral thesis proposal titled "Proposing clinician competency guidelines for the inclusion of disability in the undergraduate medical curriculum of South Africa. An exploratory study.” As part of my research, I conducted a literature search and developed arguments to strengthen the reasons why the research I propose in my thesis is necessary. It is important that I position myself in this research. I am a South African, Caucasian, female medical doctor, with an interest in physical rehabilitation medicine and I am a person with a physical disability. Although this research study will be conducted in South Africa, I am hopeful that the findings will be transferable to medical schools across the world.

Advances in next-generation sequencing have facilitated the discovery of a multitude of long non-coding RNAs (lncRNAs) with pleiotropic functions in cellular processes, disease and viral pathogenesis. It came as no surprise when viruses were also revealed to transcribe their own lncRNAs. Among them, gammaherpesviruses, one of the three subfamilies of the Herpesviridae, code their largest number. These structurally and functionally intricate non-coding (nc) transcripts modulate cellular and viral gene expression to maintain viral latency or prompt lytic reactivation. The lncRNAs allow the virus to escape cytosolic surveillance, sequester and re-localize essential cellular factors and modulate the cell cycle and proliferation. Some viral lncRNAs act as “messenger molecules”, transferring information about viral infection to neighboring cells. This broad range of lncRNA functions is achieved through lncRNA structure-mediated interactions with effector molecules of viral and host origin, including other RNAs, proteins and DNAs. In this review, we discuss examples of gammaherpesvirus-encoded lncRNAs, emphasize their unique structural attributes, and link them to viral life cycle, pathogenesis and disease progression. We will address their potential as novel targets for drug discovery and propose future directions to explore lncRNA structure and function relationship.

Retinoic acid (RA) is the biologically active metabolite of vitamin A and has become a well-established factor that induces neurite outgrowth and regeneration in both vertebrates and invertebrates. However, the underlying regulatory mechanisms that may mediate RA-induced neurite sprouting remain unclear. In the past decade, microRNAs have emerged as important regulators of nervous system development and regeneration, and have been shown to contribute to processes such as neurite sprouting. However, few studies have demonstrated the role of miRNAs in RA-induced neurite sprouting. By miRNA-Sequencing analysis, we identify 482 miRNAs in the regenerating CNS of the mollusc Lymnaea stagnalis, 219 of which represent potentially novel miRNAs. Of the remaining conserved miRNAs, 38 show a statistically significant up or downregulation in regenerating CNS as a result of RA treatment. We further characterized the expression of one neuronally-enriched miRNA upregulated by RA, miR-124. We demonstrate for the first time that miR-124 is expressed within the cell bodies and neurites of regenerating motorneurons. Moreover, we identify miR-124 expression within the growth cones of cultured ciliary motorneurons (Pedal A), whereas expression in the growth cones of another class of respiratory motorneurons (RPA) was absent in vitro. These findings support our hypothesis that miRNAs are important regulators of retinoic acid-induced neuronal outgrowth and regeneration in regeneration-competent species.

The abnormal accumulation of cells in the human brain, if left untreated, may cause brain damage. Management and treatment of these tumours require an early and accurate diagnosis, while their prognostic characterisation can also be beneficial in the choice of care planning for the patient. CDSSs are being continuously developed and integrated into routine clinical practice as they assist clinicians and radiologists to deal with an enormous amount of medical data, reduce clinical errors, and improve diagnostic capabilities. They assist detection, classification, and grading of brain tumours as well as alerting physicians of requirement of change in treatment plans. The aim of this systematic review is to identify various CDSSs used in brain tumour diagnosis and prognosis, that rely on data captured by any imaging modality. Based on the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, the literature search was conducted in PubMed and Engineering Village Compendex databases. This review examines various CDSS tool types, system features, techniques used, accuracy, and outcome, to provide the latest evidence available in the field of neuro-oncology. An overview of different types of CDSSs used to support clinical decision-making in the management and treatment of brain tumours, along with highlighting their benefits, challenges, and future perspectives has been provided.

Electric vehicles (EVs) play a significant role in reducing carbon emissions. In the US, EVs are mostly owned by multi-vehicle households, and their usage is primarily studied in the context of vehicle miles traveled. This study takes a unique approach by analyzing EV usage through the lens of vehicle choice (between EVs and internal combustion engine vehicles) within multi-vehicle households. A two-step machine-learning framework (clustering and decision trees) is proposed. The framework determines the preferred trip category for EV use and captures the effects of household attributes, driver attributes, built-environment factors, and gas prices on EV use in multi-vehicle households. Results indicate that discretionary trips (accumulated local effect = 0.037) are mostly preferred for EV use. EV preference is more pronounced among households with fewer workers (<2) and lower income levels. These findings are valuable for policymakers and auto manufacturers in targeting specific market segments and promoting EV adoption.

Tropical corals construct the three-dimensional framework for one of the most diverse ecosystems on the planet, providing habitat to a plethora of species across taxa. However, these ecosystem engineers are facing unprecedented challenges, such as increasing disease prevalence and marine heatwaves associated with anthropogenic global change. As a result, major declines in coral cover and health are being observed across the world's oceans, often due to the breakdown of coral-associated symbioses. Here, we review the interactions between the major symbiotic partners of the coral holobiont – the cnidarian host, algae in the family Symbiodiniaceae, and the microbiome – that influence trait variation, including the molecular mechanisms that underlie symbiosis and the resulting physiological benefits of different microbial partnerships. In doing so, we highlight the current framework for the formation and maintenance of cnidarian-Symbiodiniaceae symbiosis, and the role that immunity pathways play in this relationship. We emphasize that understanding these complex interactions is challenging when you consider the vast genetic variation of the cnidarian host and algal symbiont, as well as their highly diverse microbiome, which is also an important player in coral holobiont health. Given the complex interactions between and among symbiotic partners, we propose several research directions and approaches focused on symbiosis model systems and emerging technologies that will broaden our understanding of how these partner interactions may facilitate the prediction of coral holobiont phenotype, especially under rapid environmental change.

It is widely recommended to group house male laboratory mice because they are ‘social animals’, but male mice do not naturally share territories and aggression can be a serious welfare problem. Even without aggression, not all animals within a group will be in a state of positive welfare. Rather, many male mice may be negatively affected by the stress of repeated social defeat and subordination, raising concerns about welfare and also research validity. However, individual housing may not be an appropriate solution, given the welfare implications associated with no social contact. An essential question is whether it is in the best welfare interests of male mice to be group- or singly-housed. This review explores the likely impacts, positive and negative, of both housing conditions, presents results of a survey of current practice and awareness of mouse behaviour, and includes recommendations for good practice and future research. We conclude that whether group- or single-housing is better (or less worse) in any situation is highly context-dependent according to several factors including strain, age, social position, life experiences, and housing and husbandry protocols. It is important to recognise this and evaluate what is preferable from animal welfare and ethical perspectives in each case.

Lipid-based drugs are emerging as an interesting class of novel anticancer drugs with the potential to target specific cancer cell metabolic pathway linked to their proliferation and invasiveness. In particular, ω−3 polyunsaturated fatty acids (PUFA) derivatives such as epoxides and their bioisosteres have demonstrated the potential to suppress growth and promote apoptosis in triple-negative human breast cancer cells MDA-MB-231. In this study 16-(4’-chloro-3’-trifluorophenyl)carbamoylamino]hexadecanoic acid (ClFPh-CHA), an anticancer lipid derived from ω−3,17,18-epoxyeicosanoic acid, was formulated as a stable nanoemulsion with size around 150 nm and narrow droplet size distribution (PDI<0.200) through phase-inversion emulsification process followed by high pressure homogenization in view of an oral administration. The ClFPh-CHA-loaded nanoemulsions were able to significantly decrease the relative tumor volume in mice bearing an intramammary tumor xenograft at all doses tested (2.5, 10 and 40 mg/kg) after 32 days of daily oral administration. Furthermore, absolute tumor weight was decreased to 50% of untreated control at 10 and 40 mg/kg, while intraperitoneal administration could achieve a significant reduction only at the highest dose of 40 mg/kg. Results suggest that oral administration of ClFPh-CHA formulated as a nanoemulsion has a sufficient bioavailability to provide an anticancer effect in mice and that the activity is at least equal if not superior to that obtained by a conventional parenteral administration of equivalent doses of the same drug.

The ethics of invertebrate research have largely been ignored compared to the consideration of higher order animals, but more recent focus has questioned this trend. Using biohybrid robotic jellyfish as a case study, we examine the ethical considerations of invertebrate work and provide recommendations for future guidelines. This paper starts with an overview of philosophical views of animal ethics, the current state of knowledge for invertebrate pain and nociception, and current ethical guidelines. Next, we delve into the case study and analogous precedents. Specifically, in prior studies, we developed biohybrid robotic jellyfish, which modified live moon jellyfish with microelectronic swim controllers for future applications in ocean monitoring. Although jellyfish possess no central nervous system, pain receptors, or nociceptors, we closely monitored their stress responses, using the precautionary and minimization principles in consideration of the 4Rs: reduction, replacement, refinement, and reproducibility. We also discuss ethical considerations related to our studies and suggest that public opinion of invertebrate research relies heavily on repugnance, including fears of ‘playing God’ or limiting the ‘free will’ of animals. These issues are also examined for prior bioethics cases, such as the RoboRoach, cyborg beetle, ‘microslavery’ of microbes, biohybrid robots incorporating tissues from sea slugs (which are known to possess nociceptors), and other tissue cutting experiments involving soft-bodied invertebrates. However, biohybrid robotic jellyfish pose further ethical questions of potential ecological consequences as ocean monitoring tools, such as the impact of electronic waste in the ocean. To conclude these evaluations, we recommend that publishers require brief ethical statements for invertebrate research, which can include the following: a scientific justification for the research, discussion of the 4Rs, and cost-benefit analysis. We also delineate the need for more research on pain and nociception in invertebrates, which can then be used to revise or validate current research standards. These actions provide a stronger basis for the ethical study of invertebrate species, with implications for individual, species-wide, and ecological impacts on animals, as well as for interdisciplinary studies in science, engineering, and philosophy.

Despite the recognized benefits of fecal occult blood test (FOBT) and mammography screenings, participation in breast (BC) and colorectal cancer (CRC) screening programs is still suboptimal. This study investigates municipal characteristics associated with their BC/CRC screening uptake profiles among women aged 55–69 years. Using data from 308 municipalities of Flanders from 2014 to 2017, a profile for each municipality based on its BC/CRC screening uptake compared with the median screening uptake was created. Logistic regression with generalized estimating equations was used to assess the associations between municipal characteristics and BC/CRC screening uptake profiles. The overall median uptake of cancer screening was higher for CRC (57.4%) than for BC (54.6%). The following municipal characteristics were associated with worse performance in terms of only CRC, only BC, or both CRC and BC screening uptake, respectively: foreign nationality, self-employment rate, (early) retirement rate, diabetes, disabilities; (early) retirement rate; age group 65–69, foreign nationality, self-employment rate, (early) retirement rate, wage-earners, diabetes. The following municipal characteristics were associated with better performance in terms of only CRC, only BC, or both CRC and BC screening uptake respectively: residential stability, having a partner, having children, jobseeker rate, GP visits, preventive dental visits; having children, GP visits; age group 55–59, residential stability, having a partner, having children, jobseeker rate, higher education, GP visits, preventive dental visits. This study’s results regarding the interrelation between the BC and CRC screening could be used to tailor interventions to improve the participation of the target population in both programs.

There is a growing need to utilize community interventions to address modifiable behaviors that lead to poor health outcomes like obesity, diabetes, and heart disease. Poor health outcomes can be tied to community-level factors such as food deserts (identified areas with low access to fresh fruit, vegetables, and other healthful whole foods) and individual behaviors like sedentary lifestyles, consuming large portion sizes, and eating high-calorie fast food and processed foods. Through a social ecological approach with family, organization and community, the Faithful Families Cooking and Eating Smart (FFCES) intervention was created to address these concerns in a rural South Carolina community. FFCES used gatekeepers to identify 18 churches and 4 apartment complexes in low-income areas. 176 participants completed both pre- and post- survey measures. Student’s t-test measures found statistically significant change in participant perception of food security (0.39, p-value=0.005), self-efficacy with physical activity and healthy eating (0.26, p-value=000), and cooking confidence (0.17, p-value=.01). There was not significant change in cooking behaviors as assessed through the Cooking Behaviors Scale. FFCES shows that a social ecological approach can be effective at increasing and improving individual healthy behaviors and addressing community-level factors in low-income rural communities.

Despite the extensive research conducted on ruminal methanogens and anti-methanogenic intervention strategies over the last 50 years, most of the currently researched enteric CH4 abatement approaches have shown limited efficacy. This is largely because of the complex nature of animal production and the ruminal environment, host genetic variability of CH4 production, and an incomplete understanding of the role of the ruminal microbiome in enteric CH4 emissions. Recent sequencing-based studies suggest the presence of methanogenic archaea in extra-gastrointestinal tract tissues, including respiratory and reproductive tracts of cattle. While these sequencing data require further verification by culture-dependent methods, the consistent identification of methanogens with relatively greater frequency in the airway and urogenital tract of cattle plus increasing appreciation of the microbiome-gut-organ axis highlight the potential interactions between ruminal and extra-gastrointestinal methanogenic communities. Thus, a traditional singular focus on ruminal methanogens may not be sufficient, and a holistic approach which takes into consideration of the transfer of methanogens between ruminal, extra-gastrointestinal, and environmental microbial communities is of necessity to develop more efficient and long-term ruminal CH4 mitigation strategies. In the present review, we provide a holistic survey of the methanogenic archaea present in different anatomical sites of cattle and discuss potential seeding sources of the ruminal methanogens.

Body image disturbance (BID) involves negative attitudes towards shape and weight and is associated with lower levels of interoception (awareness of and attention toward internal physiological states). This association is considered a risk factor for developing eating disorders (EDs) and is linked to altered sensorimotor representations of the body (i.e., body schema). BIDs manifest across genders and are currently understudied in men. This study investigated gender-related differences in BID and its relationship to the body schema and interoception. Data were collected from 86 men and women. BID was assessed using questionnaires measuring self-objectification, state, and trait body dissatisfaction. Interoceptive sensibility was measured via the MAIA-2. The body schema was indexed via an embodied mental rotation task. Results showed that women reported higher BID than men across all scales. Gender differences in sub-components of interoceptive sensibility were found. Overall, both gender and interoceptive sensibility predicted BID. However, interoceptive sensibility exhibited its own unique association with BID beyond the influence of gender. BID, IS and gender were not significant predictors of performance in the body schema task. Therefore, while gender predicts differences in BID and interoceptive sensibility, there was no evidence of gender-related differences in body schema.

Machine learning (ML) offers potential opportunities to enhance the learning, teaching and assessments within veterinary medical education including but not limited to assisting with admissions processes as well as student progress evaluations. The purpose of this primer is to assist veterinary educators in appraising and potentially adopting these rapid upcoming advances in data science and technology. In the first section, we introduce ML concepts and highlight similarities/differences between ML and classical statistics. In the second section, we provide a step-by-step worked example using simulated veterinary student data to answer a hypothesis driven question. Python syntax with explanations is provided within the text to create a random forest ML prediction model and within each step, specific considerations such as how to manage incomplete student records are highlighted when applying ML algorithms within the veterinary education field. The results from the simulated data demonstrate how decisions by the veterinary educator during ML model creation may impact the most important features contributing to the model. These results highlight the need for the veterinary educator to be fully transparent during the creation of ML models and future research is needed to establish guidelines for handling data not missing at random in medical education, and preferred methods for model evaluation.

Legumes develop root nodules that harbour endosymbiotic bacteria, rhizobia. These rhizobia convert nitrogen to ammonia by biological nitrogen fixation. A thorough understanding of the biological nitrogen fixation in legumes and its regulation is key to develop sustainable agriculture. It is well known that plant hormones affect nodule formation; however, most studies are limited to model legumes due to their suitability for in vitro, plate-based assays. Specifically, it is almost impossible to measure the effects of exogenous hormones or other additives during nodule development in crop legumes such as soybean as they have huge root system in soil. To circumvent this issue, the present research develops suitable media and growth conditions for efficient nodule development under in vitro, soil free conditions in an important legume crop, soybean. Moreover, we also evaluate the effects of all major phytohormones during soybean nodulation under identical conditions. This versatile, inexpensive, scalable and simple protocol provides several advantages over previously established methods. It is extremely time-and resource-efficient, does not require special training or equipment, and produces highly reproducible results. The approach is expandable to other large legumes as well as for other exogenous additives.

Mucus plugging of the respiratory tract occurs in airway diseases, including asthma, chronic obstructive pulmonary disease and cystic fibrosis. It can cause blockage of airways, leading to breathlessness and lung failure. Here, we demonstrate the effect of BromAc® in dissolving mucus plugs in an novel ex-vivo ovine obstructive lung model using a ventilatory setup. Mucus simulant was filled into the trachea of freshly slaughtered ovine lungs and ventilated via an endotracheal tube (ETT) using Continuous Mandatory Ventilation. Predetermined single or repeated doses of Bromelain, Acetylcysteine (Ac), BromAc® and saline control were administered via an Aerogen® vibrating nebuliser and ventilated for 30 or 60 minutes. Ventilatory recording of resistance, compliance, tidal volume was conducted and rheology pre and post treatment were measured. A significant decline in airway resistance (p&lt;0.0001) compared to saline control was observed when treated with Bromelain, Ac and BromAc®, with the latter showing a stronger mucolytic effect than single agents. The decline in resistance was also effective in shorter timepoint (p&lt;0.05) at lower doses of the drugs. Changes in compliance, peak pressure and tidal volume was not observed post-administration of the drugs. Rheology measurements revealed that BromAc®™ significantly reduced the viscosity of the mucin at the end of 30-minute and 60-minute time points (p&lt;0.001) compared to the saline control. BromAc® showed complete dissolution of the respiratory mucus simulant and improved ventilatory airflow parameters in the ex-vivo ovine model.

In an era of unparalleled technical advancement, the pharmaceutical industry is struggling to transform data into increased research and development efficiency, and as a corollary, new drugs for patients. Here, we briefly review some of the commonly discussed issues around this counterintuitive innovation crisis. Looking at both industry and science related factors, we posit that traditional preclinical research is front-loading the development pipeline with data and drug candidates that are unlikely to succeed in patients. Applying a first principles analysis, we highlight the critical culprits and provide suggestions as to how these issues can be rectified through pursuit of a Human Data-driven Discovery (HD3) paradigm. Consistent with other examples of disruptive innovation, we propose that new levels of success are not dependent on new inventions, but rather the strategic integration of existing data and technology assets. In support of these suggestions, we highlight the power of HD3, through recently published proof-of-concept applications in the areas of drug safety analysis and prediction, drug repositioning, rational design of combination therapies and the global response to the Covid19 pandemic. We conclude that innovators must play a key role in expediting the path to a largely human focused, systems-based approach to drug discovery and research.

Background: The incidence of spinal metastatic disease has risen with improved cancer survivorship. Separation surgery, the current standard surgical treatment, does not fully address spinal deformity. Advances in operative management warrant reevaluating maximal tumor resection and anterior column reconstruction with corpectomy. Methods: An IRB-approved retrospective single-center review of 63 patients was performed. Demographics, tumor characteristics, clinical and radiographic data, treatments, and neurological and survival outcomes were analyzed. Results: The mean age at presentation was 63.5 ± 9.6 years (range, 37-84 years) and 28 patients (44.4%) were female. Functional outcomes, measured by KPS, RAND-36 survey scores and Oswestry Disability Index all improved postoperatively (pre- vs postop: 70 to 80 (p=0.0056), 26.5 to 46.4 (p=0.0081), and 28.9 to 16.9 (p=0.0613), respectively). Spinal alignment also improved, with Cobb angle measurements showing a reduction in spinal kyphosis from -5 to 0 (p=0.021). Nine patients (14.5%) had non-fatal postoperative complications. The median OS for this cohort was 14.4 months (range, 0.6-145.0 months) with median follow-up time of 15.5 months. Conclusion: In oligometastatic spinal disease patients with good functional status, corpectomy for decompression of neural elements, deformity correction, and spinal stabilization is associated with improvements in pain and functional outcomes without overwhelming morbidity.

Neosporosis is an infection caused by the protozoan parasite Neospora caninum and has substantial veterinary hazards. Neosporosis cannot be controlled via vaccination or a chemotherapeutic agent. Thus, accurate diagnosis followed by isolation and culling of infected animals is regarded as the most efficient way of control. In vivo diagnosis often relies on serologic testing of the animals, and milk represents a non-invasive and easy to collect sample matrix. However, ELISAs specifically designed for the antibody detection in milk are sometimes not easily available and it is tempting to use ELISA kits designed for use in serum also for milk samples. Herein, we evaluated a widely used commercial ELISA (ID Screen® Neospora caninum competition Multispecies ELISA (ID. Vet, Grabels, France)), developed for detection of N. caninum antibodies in serum samples, for its performance with milk samples instead. Milk samples from dairy ruminants (cows, buffaloes, sheep, goats; n = 149) were tested in parallel with the serum ELISA and a commercial milk ELISA as a standard test (Neospora caninum Milk Competitive ELISA, ID. Vet, Grabels, France). The detected prevalence rates were 42 (28.2%), 26 (17.4%), and 26 (17.4%) using milk ELISA, serum ELISA, and both ELISAs, respectively. Sensitivity, specificity, positive predictive value, and negative predictive value for the serum ELISA used with milk samples were 61.9%, 100%, 100%, 87%, respectively: Agreement and Kappa value between the two ELISAs were 89.3%, and 0.70, respectively. High values of Pearson correlation coefficient (0.991) and area under ROC curve (0.789) demonstrated a high diagnostic performance of serum ELISA also in milk samples. Also, Bland-Altman plot and Histogram describing the frequency of distribution of ELISA optical densities confirmed the high agreement of both serum and milk ELISAs. The current results revealed a high specificity but moderate sensitivity of the serum ELISA used for milk samples compared with the milk ELISA. However, the excellent positive predictive value of the serum ELISA makes it an alternative option in case of unavailability of milk ELISA. With this study, we provided additional evidence that a widely used serum ELISA test kit may also be used for detection of N. caninum antibodies in milk samples.

The United Nations Convention on the Rights of Persons with Disabilities (hereafter CRPD) has provided a radical imperative for the reform of mental health and capacity legislation around the world. The interpretation of the CRPD has been controversial, ranging from complete abolition of detention, forcible treatment and substitute decision making, to acceptance that elements of these measures need to be retained but based on non-discriminatory criteria, additional safe-guards and a comprehensive shift towards supported decision-making. While the potential ef-fects of the CRPD on mental health social work and social work generally are considerable given their shared commitment towards social justice, to date there has been no review of research evi-dence exploring their relationship. In addressing this knowledge gap, this study held a prelimi-nary discussion with practitioners and academics at the European Association of Social Work Mental Health Special Interest Group in Amsterdam 2022, followed by a scoping literature re-view on the question: What impact, if any, has the CRPD had on social work practice? The review produced four main findings: impact on legislation; positive impact on practice; limited impact on practice; and impact on social work education and research. In sum, while there were some positive indications of social work and mental health social work practice being influenced by the CRPD, these were scant. Barriers to change included tendencies among some social workers to practise substitute decision-making, in part related to resourcing and policy contexts, and under-standings of disability aligned to individualised/medical rather than social perspectives. The results indicate that legal reform on its own is insufficient to impact social work practice, and that realising the potential of the CRPD will necessitate good quality training, as well as improv-ing social workers’ knowledge of the human rights of people with mental impairment.

Profiling technologies, such as proteomics, allow the simultaneous measurement and comparison of thousands of plant components without prior knowledge of their identity. The combination of these non-targeted methods facilitates a more comprehensive approach than targeted methods and thus provides additional opportunities to identify genotypic changes resulting from genetic modification, including new allergens or toxins. The purpose of this study was to investigate unintended changes in GM Bt maize grown in South Africa. In the present study, we used bi-dimensional gel electrophoresis based on fluorescence staining, coupled with mass spectrometry in order to compare the proteome of the field-grown transgenic hybrid (MON810) and its near-isogenic counterpart. Proteomic data showed that energy metabolism and redox homeostasis were unequally modulated in GM Bt and non-GM maize variety samples. In addition, a potential allergenic protein – pathogenesis related protein -1 has been identified in our sample set. These finding highlight the suitability of unbiased profiling approaches to complement current GMO risk assessment practices worldwide.

In Belgium, silages are often infected by Penicillium roqueforti sensu lato (s.l.). These toxigenic fungi are well adapted to silage conditions, and their prevention during feed-out is difficult. Bacillus velezensis strain NRRL B-23189 has been reported to inhibit P. roqueforti s.s. conidiospore germination in vitro by the production of lipopeptides. In the present study, the antagonistic effect of this B. velezensis strain towards P. roqueforti s.l. was evaluated in vitro and in vivo. In vitro, corn silage conditions were simulated, and the impact of B. velezensis culture supernatant or cell suspension on P. roqueforti s.l. growth, conidiospore germination and survival and roquefortine C production was evaluated. The antagonism was promising, but growth of B. velezensis in corn silage infusion was poor. An in vivo experiment with microsilos containing a mixture of perennial ryegrass and white clover artificially contaminated with P. roqueforti s.l. was carried out to determine if B. velezensis cell suspension could be used as an antagonistic silage inoculant. The B. velezensis cell suspension applied was unsuccessful in reducing P. roqueforti s.l. numbers at desiling after 56 days compared to no additive application. However, feed-out of the silage was not simulated, so it remains elusive whether or not B. velezensis exerts antagonistic activity during this phase.

Necroptosis is an inflammatory form of lytic programmed cell death that is thought to have evolved to defend against pathogens. Genetic deletion of the terminal effector protein – MLKL – shows no overt phenotype in the C57BL/6 mouse strain under conventional laboratory housing conditions. Small molecules that inhibit necroptosis by targeting the kinase activity of RIPK1, one of the main upstream conduits to MLKL activation, have shown promise in several murine models of non-infectious disease and in phase II human clinical trials. This has triggered multi-billion-dollar investments into the emerging class of necroptosis blocking drugs, and the potential utility of targeting the terminal effector is being closely scrutinised. Here we review murine models of disease, both genetic deletion and mutation, that investigate the role of MLKL. We summarize a series of examples from several broad disease categories including ischemia reperfusion injury, sterile inflammation, pathogen infection and haematological stress. Elucidating MLKL’s contribution to mouse models of disease is an important first step to identify human indications that stand to benefit most from MLKL-targeted drug therapies.

Immobilized metal affinity chromatography (IMAC) is a popular and valuable method for the affinity purification of polyhistidine-tagged recombinant proteins. However, it often shows practical limitations, which might require cumbersome optimizations, additional polishing, and enrichment steps. Here, we present functionalized corundum particles for the efficient, economical, and fast purification of recombinant proteins in a column-free format. The corundum surface is first derivatized with the amino silane APTES, then EDTA dianhydride, and subsequently loaded with nickel ions. The Kaiser test, well-known in solid-phase peptide synthesis, was used to monitor amino silanization and the reaction with EDTA dianhydride. In addition, ICP-MS was performed to quantify the metal-binding capacity. His-tagged protein A/G (PAG), mixed with bovine serum albumin (BSA), was used as a test system. The PAG binding capacity was around 3 mg protein per gram of corundum. Cytoplasm obtained from different E. coli strains was examined as an example of a complex matrix. The imidazole concentration was varied in the loading and washing buffers. As expected, higher imidazole concentrations during loading are usually beneficial when higher purities are desired. Even when higher sample volumes, such as one liter, were used, recombinant protein down to a concentration of 1 µg/mL could be isolated selectively. Comparing the corundum material with standard Ni-NTA agarose beads indicated higher purities of proteins isolated using corundum. His6-MBP-mSA2, a fusion protein consisting of monomeric streptavidin and maltose-binding protein in the cytoplasm of E. coli, was purified successfully. To show that this method is also suitable for mammalian cell culture supernatants, purification of the SARS-CoV-2-S-RBD His8 expressed in human Expi293F cells was performed. The material cost of the nickel-loaded corundum material (without regeneration) is estimated to be less than 30 cents for 1 gram of functionalized support or 10 cents per milligram of isolated protein. Another advantage of the novel system is the corundum particles' extremely high physical and chemical stability. The new material should be applicable in small laboratories and large-scale industrial applications. In summary, we could show that this new material is an efficient, robust, and cost-effective purification platform for the purification of His-tagged proteins, even in challenging, complex matrices and large sample volumes of low product concentration.

Oral cancer cells (TYS) and the signalling pathways involved in metastasis, in response to cancer-associated fibroblasts (CAFs, COM) and normal oral mucosal fibroblasts (MM1) was studied. Metastatic cell behaviour was observed by cell-scatter, 3D-collagen gel migration and 3D-spheroid invasion assays. Akt, MAPK, EGFR, TGFβRii and CXCR4 inhibitors were used to identify the signalling pathways involved. Signalling pathway protein expression and activation were assessed by SDS-PAGE and Western Blotting. COM-CM (conditioned medium) and MM1-CM stimulated cancer cell scattering, which was blocked only by the Akt inhibitor. COM-CM induced scattered cancer cells showed higher levels of Akt phosphorylation than the negative control and MM1-CM. Migration and invasion of TYS cells into the collagen gels from the spheroids was stimulated by CM from both sources, compared to the negative control. COM cells stimulated TYS, cancer cell invasion into the collagen more than MM1 and the control. Akt and EGFR inhibitors effectively blocked CM and COM cell-induced invasion. Akt-silenced cancer cells were not stimulated to migrate and invade by fibroblast-CM and did not survive addition of the EGFR inhibitor. This suggests that CAFs stimulate oral cancer cell migration and invasion in an Akt- dependent manner. EGFR and Akt are potential therapy targets in metastatic oral cancer.

Atherosclerosis is a leading cause of cardiovascular disease and mortality worldwide. Alterations in the gut microbiota composition, known as gut dysbiosis, have been shown to contribute to atherosclerotic cardiovascular disease (ACVD) development through several pathways. Disruptions in gut homeostasis are associated with activation of immune processes and systemic inflammation. The gut microbiota produces several metabolic products, namely trimethylamine (TMA), which is used to produce the proatherogenic metabolite trimethylamine-N-oxide (TMAO). Short chain fatty acids (SCFAs), including acetate, butyrate, and propionate, and certain bile acids (BAs) produced by the gut microbiota lead to inflammation resolution and decrease atherogenesis. Chronic low-grade inflammation is associated to common risk factors for atherosclerosis, including metabolic syndrome, type 2 diabetes mellitus (T2DM), and obesity. Novel strategies for reducing ACVD include the use of nutraceuticals such as resveratrol, modification of glucagon-like peptide 1 (GLP-1) levels, supplementation with probiotics, and administration of prebiotic SCFAs and BAs. Investigation into the relationship between the gut microbiota and its metabolites, and the host immune system could reveal promising insight into ACVD development, prognostic factors, and treatments.

Hoof capability of domesticated, barefoot-kept horses and ponies traversing artificial environments remains undocumented. In this study, four equines were walked in-hand for 16 days, covering a distance of 50 km, over three solid surfaces. Subsequently, we conducted an assessment of hoof morphology. Hooves (n = 16) were radiographed before and after the trial, spaced 3 weeks apart, for sole depth measurement. External measurements of feet were recorded 24 hours before day 1 and repeated on day 9. Radiographs revealed increased sole depth in 11 hooves, notably at the palmar process, and some misalignment in certain phalanges. On day 9, after a 36-km distance, all hooves exhibited calloused soles and frogs, and required trimming. The front hooves of the horses had a pronounced, natural concavity. Hard surfaces were found to stimulate sole growth, with a portion of sole thickness preferentially accumulating within the dermal zone. Collectively, the maintenance of short trimming cycles to prevent misalignment, minimize hoof-wall loading and maintain a load-sharing system, may be necessary for barefoot-kept horses considering their rapid growth rate.