Search

ABSTRACT Biomarkers of kidney function, including glomerular, tubular, and fibrotic markers, have been associated with blood pressure in elderly populations and individuals with kidney and cardiovascular diseases. However, limited information is available in young adults. In this study, we compared levels of several kidney function biomarkers between normotensive and hypertensive young adults and explored the associations of these biomarkers with blood pressure within these groups. In this cross‐sectional assessment, twenty‐four‐hour (24‐h) blood pressure measurements of 1055 participants (mean age = 24.6 years) were used to classify hypertension as per the 2018 ESC/ESH guidelines. Biomarkers of kidney function included estimated glomerular filtration rate, urinary albumin, alpha‐1 microglobulin (uA1M), neutrophil gelatinase‐associated lipocalin (uNGAL), uromodulin (uUMOD), and the CKD273 classifier. All urinary biomarkers, except for the CKD273 classifier, were standardized for urinary creatinine (Cr). In the hypertensive group (61.0% White; 73.2% men), urinary albumin‐to‐creatinine ratio (uACR), uNGAL/Cr and uUMOD/Cr were lower than the normotensive group. In multiple regression analyses, 24‐h systolic blood pressure (SBP) (β = 0.14; p = 0.042), 24‐h diastolic blood pressure (DBP) (β = 0.14; p = 0.040), and 24‐h mean arterial pressure (MAP) (β = 0.16; p = 0.020) associated positively with uA1M/Cr in the hypertensive group, while 24‐h MAP positively associated with uACR (β = 0.17; p = 0.017). In exploratory factor analysis, positive associations of 24‐h DBP and 24‐h MAP with a factor pattern including tubular biomarkers were observed in the hypertensive group (24‐h DBP: β = 0.18; p = 0.026, 24‐h MAP: β = 0.17; p = 0.032). In the setting of hypertension, high perfusion pressure in the kidneys may play a role in the development of proximal tubule damage and promote early deterioration in kidney function in young adults. Trial Registration: ClinicalTrials.gov identifier: NCT03292094

Abstract Objective This study investigates the geographical distribution of private hospitals in Australian capital cities in relation to the Index of Relative Socioeconomic Disadvantage. Methods Using Geographic Information System analysis, the study examined how private hospitals are distributed across different socioeconomic quartiles, providing a comprehensive visualisation of health care accessibility. Results The results indicate an unequal distribution with a substantial concentration of private hospitals within the vicinity of communities classified in the highest socioeconomic classification. This raises significant concerns about health care equity, particularly in light of the increased strain on health care systems before, during and after the COVID‐19 pandemic. Conclusions This study underscores the need for targeted policy interventions to enhance the resilience and accessibility of the private health care sector, specifically targeting disadvantaged communities. It suggests that comprehensive, geographically‐informed data is crucial for policymakers to make informed decisions that promote health equity in the postpandemic landscape.

Abstract Pharmacogenomic (PGx) biomarkers integrated using machine learning can be embedded within the electronic health record (EHR) to provide clinicians with individualized predictions of drug treatment outcomes. Currently, however, drug alerts in the EHR are largely generic (not patient‐specific) and contribute to increased clinician stress and burnout. Improving the usability of PGx alerts is an urgent need. Therefore, this work aimed to identify principles for optimal PGx alert design through a health‐system‐wide, mixed‐methods study. Clinicians representing multiple practices and care settings (N = 1062) in urban, rural, and underserved regions were invited to complete an electronic survey comparing the usability of three drug alerts for citalopram, as a case study. Alert 1 contained a generic warning of pharmacogenomic effects on citalopram metabolism. Alerts 2 and 3 provided patient‐specific predictions of citalopram efficacy with varying depth of information. Primary outcomes included the System's Usability Scale score (0–100 points) of each alert, the perceived impact of each alert on stress and decision‐making, and clinicians' suggestions for alert improvement. Secondary outcomes included the assessment of alert preference by clinician age, practice type, and geographic setting. Qualitative information was captured to provide context to quantitative information. The final cohort comprised 305 geographically and clinically diverse clinicians. A simplified, individualized alert (Alert 2) was perceived as beneficial for decision‐making and stress compared with a more detailed version (Alert 3) and the generic alert (Alert 1) regardless of age, practice type, or geographic setting. Findings emphasize the need for clinician‐guided design of PGx alerts in the era of digital medicine.

Abstract Feedstock variability represents a challenge in lignocellulosic biorefineries, as it can influence both lignocellulose deconstruction and microbial conversion processes for biofuels and biochemicals production. The impact of feedstock variability on microbial performance remains underexplored, and predictive tools for microbial behaviour are needed to mitigate risks in biorefinery scale‐up. Here, twelve batches of corn stover were deconstructed via deacetylation, mechanical refining, and enzymatic hydrolysis to generate lignin‐rich and sugar streams. These batches and their derived streams were characterised to identify their chemical components, and the streams were used as substrates for producing muconate and butyrate by engineered Pseudomonas putida and wildtype Clostridium tyrobutyricum, respectively. Bacterial performance (growth, product titers, yields, and productivities) differed among the batches, but no strong correlations were identified between feedstock composition and performance. To provide metabolic insights into the origin of these differences, we evaluated the effect of twenty‐three isolated chemical components on these microbes, including three components in relevant bioprocess settings in bioreactors, and we found that growth‐inhibitory concentrations were outside the ranges observed in the streams. Overall, this study generates a foundational dataset on P. putida and C. tyrobutyricum performance to enable future predictive models and underscores their resilience in effectively converting fluctuating lignocellulose‐derived streams into bioproducts.

Abstract About one decade after the first report on MXenes, these 2D early transition metal carbides or nitrides have become among the best‐performing materials in electrode applications related to electrical energy storage devices and power‐to‐fuels conversion. MXenes are obtained by a top‐down approach starting from the appropriate 3D MAX phase that undergoes etching of the A‐site metal. Initial etching procedures are based on the use of concentrated HF or the in situ generation of this highly corrosive and poisonous reagent. Etching of the MAX phase is one of the major hurdles limiting the progress of the field. The present review summarizes an alternative, universal, and easily scalable etching procedure based on treating the MAX precursor with a Lewis acid molten salt. The review starts with presenting the current state of the art of the molten salt etching procedure to obtain or modify MXene, followed by a summary of the applications of these MXene samples. The aim of the review is to show the versatility and advantages of molten salt etching in terms of general applicability, control of the surface terminal groups, and uniform deposition of metal nanoparticles, among other features of the procedure.

Abstract Lions (Panthera leo) are declining across their range, mainly due to human‐induced habitat fragmentation and prey depletion. However, the South African lion population continues to grow. Unlike other range states, South Africa actively manages wild lions across a continuum of landscapes and ecological constraints. Many of these lions are in small, fenced reserves where managers seek to mimic ecological processes in small landscapes. However, the effectiveness of this management approach has not been evaluated against meta‐population criteria. Given that meta‐population dynamics allows species living in fragmented habitats to persist, we evaluated how South Africa's lion population complies with meta‐population criteria using national audit data between 2010 and 2019 from 49 fenced, wild lion reserves. The small, fenced reserves holding wild lions fulfil the criteria for meta‐population functionality. However, this functionality was achieved through haphazard and uncoordinated management actions and not through a coordinated approach. Our main recommendation is to consider implementing a more coordinated meta‐population management approach. At the very least, meta‐population management guidelines should be reviewed and updated on a regular basis, regular audits should be conducted and periodic genetic evaluation of the meta‐population (every 10 years) should be instituted. We recommend incentivising lion managers to enhance the conservation of lions in South Africa within a meta‐population framework. We also recommend a focus on improving decision making and policy procedures that facilitates compliance with relevant legislation aimed at achieving high levels of lion conservation‐governance efficiency. South Africa's meta‐population approach to wild lion management in small, fenced reserves is effective at conserving lions and contributing to lion conservation more broadly. In an increasingly fragmented landscape, the need for human management actions to ensure persistence of large carnivores is likely to increase. A managed meta‐population approach of fenced (or unfenced, but geographically isolated) populations is a useful tool for conservationists to consider worldwide.

Abstract Objective The advent of the COVID‐19 pandemic has accentuated the critical importance of epidemic preparedness within national healthcare systems. This study presents a geospatial analysis aimed at optimising the placement of field hospitals in Australia to ensure adequate healthcare access during pandemics. Methods The latest census data from the Australian Bureau of Statistics were integrated with the spatial locations of current emergency departments within Australian capitals. Buffer zones with a 7.5 km radius were created around the public emergency departments (EDs). Buffer zones outside the 7.5 km radius that exhibited high population densities were categorised into high‐density (red), moderate‐density (yellow) and low‐density (green) zones to prioritise and tailor healthcare responses during a pandemic. The identification of high‐density population areas outside the ED radius enabled the stratification of potential sites for ED facilities. Results Ninety‐one potential field hospital sites were identified across Australia's capital cities. The findings indicate that the addition of these sites would place over 95% of the population within a 7.5 km radius of an ED facility. This network of proposed sites is designed to serve a spectrum of population densities, ensuring equitable healthcare access for both densely populated urban centres and less populated areas. Conclusions This study underscores the potential of field hospitals to strengthen Australia's public health system against emergencies. By advocating for the creation of 91 field hospitals within a 7.5 km reach for over 95% of urban dwellers across major cities, it demonstrates a strategic approach to ensure comprehensive ED coverage. Drawing on international examples, including China's Fangcang hospitals, the USA's post‐acute care (PAC) facilities and the United Kingdom's National Health Service (NHS) Nightingale Hospitals, it highlights the need for healthcare agility and scalability, especially during pandemic outbreaks. The research presents a blueprint for field hospital deployment, marking a significant advancement in public health logistics and protection across Australia's varied demographic and geographical landscapes.

Abstract The purpose of this study was to analyze technology adoption constructs that are instrumental for organizations to effectively utilize emerging technologies, enabling them to navigate the complexities and opportunities presented by the fourth industrial revolution (4IR). To achieve this a descriptive research approach was used, guided by a systematic review of literature from 2016 to 2022. Among the 4037 studies initially identified, only 69 were deemed relevant. Meta‐synthesis was then used to systematically identify, categorize, and quantify fundamental constructs inherent in the models from the relevant literature. As a result of this process, 406 constructs were identified across six thematic categories. These were subsequently integrated to develop a conceptual model that can be used to coordinate strategies to harness the potential of the 4IR towards a future‐ready business. Findings show that the role of technology adoption remains pertinent in the ever‐digitized world in which businesses operate and certain constructs are key to explain, support, and predict enterprise‐wide adoption in the 4IR paradigm. Future studies can expand and test the model to promote digital fluency required by business constituents, noting differences across sectors.

Abstract Tamoxifen, a selective estrogen receptor modulator, is used to treat hormone receptor‐positive breast cancer. Tamoxifen acts as a prodrug, with its primary therapeutic effect mediated by its principal metabolite, endoxifen. However, tamoxifen has complex pharmacokinetics involving several drug‐metabolizing enzymes and transporters influencing its disposition. Genes encoding enzymes involved in tamoxifen disposition exhibit genetic polymorphisms which vary widely across world populations. This review highlights the lack of data on tamoxifen pharmacogenetics among African populations. Gaps in data are described in this study with the purpose that future research can address this dearth of research on the pharmacogenetics of tamoxifen among African breast cancer patients. Initiatives such as the African Pharmacogenomics Network (APN) are crucial in promoting comprehensive pharmacogenetics studies to pinpoint important variants in pharmacogenes that could be used to reduce toxicity and improve efficacy.

Abstract Aim Early cancer diagnosis is necessary to improve survival rates. The aim of this study was to assess the outcome and cost of the childhood cancer training programme amongst healthcare workers. Design This was a prospective pre–post study design, using questionnaires for pre‐ and post‐training testing. The warning signs of childhood cancer were used as the main teaching content to improve recognition and early diagnosis. Methods Pre‐training and post‐training knowledge, as well as attitude questionnaires, was administered at the beginning and at the end of each training workshop. Paired samples t test and chi‐square were used to compare the change in knowledge and differences between groups. Results The overall percentage knowledge score increased from 51%–85% (p

Abstract Genetic diversity is the determinant for pest species’ success and vector competence. Understanding the ecological and evolutionary processes that determine the genetic diversity is fundamental to help identify the spatial scale at which pest populations are best managed. In the present study, we present the first comprehensive analysis of the genetic diversity and evolution of Rhopalosiphum padi, a major pest of cereals and a main vector of the barley yellow dwarf virus (BYDV), in England. We have used a genotyping‐by‐sequencing approach to study whether (a) there is any underlying population genetic structure at a national and regional scale in this pest that can disperse long distances; (b) the populations evolve as a response to environmental change and selective pressures; and (c) the populations comprise anholocyclic lineages. Individual R. padi were collected using the Rothamsted Insect Survey's suction‐trap network at several sites across England between 2004 and 2016 as part of the RIS long‐term nationwide surveillance. Results identified two genetic clusters in England that mostly corresponded to a North–South division, although gene flow is ongoing between the two subpopulations. These genetic clusters do not correspond to different life cycle types, and cyclical parthenogenesis is predominant in England. Results also show that there is dispersal with gene flow across England, although there is a reduction between the northern and southern sites with the south‐western population being the most genetically differentiated. There is no evidence for isolation by distance and other factors such as primary host distribution, uncommon in the south and absent in the south‐west, could influence the dispersal patterns. Finally, results also show no evidence for the evolution of the R. padi population, and it is demographically stable despite the ongoing environmental change. These results are discussed in view of their relevance to pest management and the transmission of BYDV.

We determined whether progression‐free survival (PFS) in metastatic breast cancer (MBC) patients receiving everolimus plus exemestane (EVE/EXE) varies depending on circulating tumour DNA (ctDNA) characteristics. Baseline plasma cell‐free DNA (cfDNA) from 164 postmenopausal women with ER‐positive, HER2‐negative MBC refractory to a nonsteroidal aromatase inhibitor and treated with standard EVE/EXE (Everolimus Biomarker Study, Eudract 2013‐004120‐11) was characterised for 10 relevant breast cancer genes by next‐generation sequencing with molecular barcoding. ctDNA molecule numbers, number of mutations and specific variants were related with PFS and overall survival (OS). Missense hotspot mutations in cfDNA were detected in 125 patients. The median of 54 ctDNA molecules per mL plasma distinguished patients with high and low/no ctDNA load. Patients with low/no ctDNA load (N = 102) showed longer median PFS of 5.7 months (P = 0.006) and OS of 124.8 months (P = 0.008) than patients with high ctDNA load (N = 62; 4.4 months and 107.7 months, respectively) in multivariate analyses. Patients with

Abstract Background Skeletal muscle is a plastic tissue that can adapt to different stimuli. It is well established that Mammalian Target of Rapamycin Complex 1 (mTORC1) signalling is a key modulator in mediating increases in skeletal muscle mass and function. However, the role of mTORC1 signalling in adult skeletal muscle homeostasis is still not well defined. Methods Inducible, muscle‐specific Raptor and mTOR k.o. mice were generated. Muscles at 1 and 7 months after deletion were analysed to assess muscle histology and muscle force. Results We found no change in muscle size or contractile properties 1 month after deletion. Prolonging deletion of Raptor to 7 months, however, leads to a very marked phenotype characterized by weakness, muscle regeneration, mitochondrial dysfunction, and autophagy impairment. Unexpectedly, reduced mTOR signalling in muscle fibres is accompanied by the appearance of markers of fibre denervation, like the increased expression of the neural cell adhesion molecule (NCAM). Both muscle‐specific deletion of mTOR or Raptor, or the use of rapamycin, was sufficient to induce 3–8% of NCAM‐positive fibres (P < 0.01), muscle fibrillation, and neuromuscular junction (NMJ) fragmentation in 24% of examined fibres (P < 0.001). Mechanistically, reactivation of autophagy with the small peptide Tat‐beclin1 is sufficient to prevent mitochondrial dysfunction and the appearance of NCAM‐positive fibres in Raptor k.o. muscles. Conclusions Our study shows that mTOR signalling in skeletal muscle fibres is critical for maintaining proper fibre innervation, preserving the NMJ structure in both the muscle fibre and the motor neuron. In addition, considering the beneficial effects of exercise in most pathologies affecting the NMJ, our findings suggest that part of these beneficial effects of exercise are through the well‐established activation of mTORC1 in skeletal muscle during and after exercise.

Abstract Background In contrast to dogs, the causes and outcomes of urinary incontinence (UI) in cats are largely unknown. Objectives To determine the causes, identify comorbid conditions, and assess outcomes of cats with micturition disorders presenting as UI. Animals Forty‐five cats with UI. Methods Retrospective study. Medical records of cats presented from January 2006 to December 2017 were searched using 45 keywords related to UI. History, presenting complaint, and physical examination findings were used to confirm a diagnosis. Cases were categorized based on functional and anatomic localizations. Results Forty‐five cats met inclusion criteria. Spinal cord disease was the most common cause of UI (n = 18), followed by urethral (n = 17), bladder (n = 9), and ureteral (n = 1) disorders. Proportions of voiding and storage phase disorders were similar (53% and 47%, respectively). However, voiding‐phase disorders were observed more frequently in males and younger‐aged cats (P

Abstract Forest and wildlife management can help regulate the risk of human exposure to tick‐borne pathogens by influencing the population density of host‐seeking ticks and the pathogen infection prevalence in tick populations. For the blacklegged tick (Ixodes scapularis), also known as the deer tick, the overall density of host‐seeking nymphs and the density of nymphs infected with Borrelia burgdorferi sensu stricto (which causes Lyme disease) are often closely and positively correlated. We sought to identify biotic and abiotic factors influencing nymph abundance in a multiscale assessment within and across forested landscapes in northern Wisconsin. On a set of randomly located plots within each of six mesic, hardwood‐dominated forests, we collected host‐seeking and on‐host ticks, observed two common mammal hosts (white‐tailed deer and mice), and characterized the structure and composition of the forest plant community. We also surveyed activity of exotic invasive earthworms, which are altering forest structure in the region. At the broader forest‐level scale (n = 6), nymphal tick abundance was positively related to deer population density after accounting for the negative influence of forb cover. At the finer plot‐level scale (n = 87), nymph abundance was positively correlated with the abundance of coarse woody debris and negatively correlated with the density of earthworm castings, an indicator of Lumbricid (nightcrawler) activity. Thus, we identified a suite of key factors, operating at different spatial scales, that shape the suitability of forest habitat for questing immature ticks. These findings inform our basic understanding of blacklegged tick ecology and also have important implications for managing tick‐borne pathogens in forest ecosystems and landscapes.

Abstract Glufosinate efficacy is inconsistent among weed species and under environmental conditions that favor rapid droplet drying. Surfactant‐humectant adjuvants could maximize glufosinate efficacy by increasing wetting and penetration into the leaf surface while decreasing evaporation rate (ER). However, there is a lack of information in the literature about the interaction of surfactant‐humectants adjuvants with glufosinate. The objective of this study was to investigate the influence of surfactant‐humectant adjuvants on the physical properties, droplet size, and efficacy of two glufosinate formulations. Laboratory, greenhouse, and field studies were conducted at the Pesticide Application Technology Laboratory of the University of Nebraska‐Lincoln. Treatment design was a 2 × 5 factorial with two glufosinate formulations combined with five adjuvant treatments plus an untreated control. Density and viscosity of glufosinate solutions mostly increased with the addition of adjuvants. However, the influence of the adjuvants on dynamic surface tension (dST), static contact angle (sCA), and evaporation rate (ER) varied by glufosinate formulation, adjuvant, and relative humidity (RH). Under greenhouse conditions, an improvement in efficacy by adding adjuvants was mainly observed for Interline solutions. The addition of adjuvants to Interline solutions increased biomass reduction up to 19 and 35% for common lambsquarters (Chenopodium album L.) and kochia [Bassia scoparia (L.) A. J. Scott], respectively. Also, some of the adjuvants presented null or antagonistic influence on herbicide efficacy. No increase in control, biomass reduction, and mortality of horseweed (Erigeron canadensis L.) and Palmer amaranth (Amaranthus palmeri S. Watson) was observed with the use of adjuvants under field conditions. Herbicide‐adjuvant‐plant‐environment interaction is complex. Thus, the use of surfactant‐humectant adjuvants may not increase herbicide efficacy.

The airway epithelial glycocalyx plays an important role in preventing severe acute respiratory syndrome coronavirus 2 entry into the epithelial cells, while the endothelial glycocalyx contributes to vascular permeability and tone, as well as modulating immune, inflammatory, and coagulation responses. With ample evidence in the scientific literature that coronavirus disease 2019 (COVID-19) is related to epithelial and endothelial dysfunction, preserving the glycocalyx should be the main focus of any COVID-19 treatment protocol. The most studied functional unit of the glycocalyx is the glycosaminoglycan heparan sulfate, where the degree and position of the sulfate groups determine the biological activity. N-acetylcysteine (NAC) and other sulfur donors contribute to the inorganic sulfate pool, the rate-limiting molecule in sulfation. NAC is not only a precursor to glutathione but also converts to hydrogen sulfide, inorganic sulfate, taurine, Coenzyme A, and albumin. By optimising inorganic sulfate availability, and therefore sulfation, it is proposed that COVID-19 can be prevented or at least most of the symptoms attenuated. A comprehensive COVID-19 treatment protocol is needed to preserve the glycocalyx in both the prevention and treatment of COVID-19. The use of NAC at a dosage of 600 mg bid for the prevention of COVID-19 is proposed, but a higher dosage of NAC (1200 mg bid) should be administered upon the first onset of symptoms. In the severe to critically ill, it is advised that IV NAC should be administered immediately upon hospital admission, and in the late stage of the disease, IV sodium thiosulfate should be considered. Doxycycline as a protease inhibitor will prevent shedding and further degradation of the glycocalyx.

Background Hyperhomocysteinemia is a risk factor for ischemic stroke; however, a targeted treatment strategy is lacking partly because of limited understanding of the causal role of homocysteine in cerebrovascular pathogenesis. Methods and Results In a genetic model of cystathionine beta synthase (CBS) deficiency, we tested the hypothesis that elevation in plasma total homocysteine exacerbates cerebrovascular injury and that memantine, a N‐methyl‐D‐aspartate receptor antagonist, is protective. Mild or severe elevation in plasma total homocysteine was observed in Cbs+/− (6.1±0.3 μmol/L) or Cbs−/− (309±18 μmol/L) mice versus Cbs+/+ (3.1±0.6 μmol/L) mice. Surprisingly, Cbs−/− and Cbs+/− mice exhibited similar increases in cerebral infarct size following middle cerebral artery ischemia/reperfusion injury, despite the much higher total homocysteine levels in Cbs−/− mice. Likewise, disruption of the blood brain barrier was observed in both Cbs+/− and Cbs−/− mice. Administration of the N‐methyl‐D‐aspartate receptor antagonist memantine protected Cbs+/− but not Cbs−/− mice from cerebral infarction and blood brain barrier disruption. Our data suggest that the differential effect of memantine in Cbs+/− versus Cbs−/− mice may be related to changes in expression of N‐methyl‐D‐aspartate receptor subunits. Cbs−/−, but not Cbs+/− mice had increased expression of NR2B subunit, which is known to be relatively insensitive to homocysteine. Conclusions These data provide experimental evidence that even a mild increase in plasma total homocysteine can exacerbate cerebrovascular injury and suggest that N‐methyl‐D‐aspartate receptor antagonism may represent a strategy to prevent reperfusion injury after acute ischemic stroke in patients with mild hyperhomocysteinemia.