Search Results (61)

Fecal water syndrome (FWS) in horses is characterized by two-phase defecation, including both solid and liquid phases. While satisfactory explanations for FWS are unavailable, bacterial dysbiosis has been suggested as a contributing or causative factor. The objectives of this study were to determine whether fecal bacterial dysbiosis is associated with FWS in horses in the midwestern USA. Fecal samples were collected from horses with FWS and from unaffected horses at the same location. In total, 16S rRNA amplicon libraries produced from fecal bacterial DNA were sequenced using the Illumina sequencing platform. Significant differences in beta diversity were detected between affected and control horses (p = 7 × 10⁻⁴, F = 1.51), and differential abundance testing identified several features enriched in affected and control horses. These results agree with prior work regarding specific features in the bacterial microbiome associated with FWS, including Alloprevotella spp., and suggest fecal dysbiosis is associated with FWS. Full article

Accurately monitoring aboveground biomass (AGB) and tree mortality is crucial for understanding forest health and carbon dynamics. LiDAR (Light Detection and Ranging) has emerged as a powerful tool for capturing forest structure across different spatial scales. However, the effectiveness of LiDAR for predicting AGB and tree mortality depends on the type of instrument, platform, and the resolution of the point cloud data. We evaluated the effectiveness of three distinct LiDAR-based approaches for predicting AGB and tree mortality in a 25.6 ha North American temperate forest. Specifically, we evaluated the following: GEDI-simulated waveforms from airborne laser scanning (ALS), grid-based structural metrics derived from unmanned aerial vehicle (UAV)-borne lidar data, and individual tree detection (ITD) from ALS data. Our results demonstrate varying levels of performance in the approaches, with ITD emerging as the most accurate for AGB modeling with a median R² value of 0.52, followed by UAV (0.38) and GEDI (0.11). Our findings underscore the strengths of the ITD approach for fine-scale analysis, while grid-based forest metrics used to analyze the GEDI and UAV LiDAR showed promise for broader-scale monitoring, if more uncertainty is acceptable. Moreover, the complementary strengths across scales of each LiDAR method may offer valuable insights for forest management and conservation efforts, particularly in monitoring forest dynamics and informing strategic interventions aimed at preserving forest health and mitigating climate change impacts. Full article

Background: To extend the practicality of liquid biopsy beyond the historical HPV circulating tumor DNA (ctDNA) assays, we evaluated the clinical relevance of a novel next-generation sequencing HPV ctDNA assay in patients with locally advanced and metastatic squamous cell cancer of the anal canal (mSCCA). Methods: ctDNA isolated from the plasma of patients with mSCCA was sequenced using a 1.4 Mb hybrid-capture target-enrichment panel covering the whole genome sequences of all 193 HPV types. The HPV type, copy number (CN), and integration sites were determined using a bioinformatic pipeline. Results: A total of 77 plasma samples from 28 patients with HPV-related SCCA were retrospectively analyzed. HPV ctDNA was detected in 26 cases (93%) (including uncommon subtypes). The median HPV CN was higher in metastatic versus locally recurrent/unresectable SCCA (p = 0.043). Changes in the HPV CN were concordant with the radiographic response (p = 0.027). An integration event was detected in 23 patients (82%), with presumed episomal HPV DNA present in the remaining patients. Higher HPV integration (a mean of ≥1 integration across samples) was associated with a worse overall survival from the start of immunotherapy (13.6 months versus 36.0 months; p = 0.003). Conclusions: Using HPV-informed next-generation sequencing of the ctDNA, we found changes in the HPV CN correlated with the treatment response and that HPV integration detected in the ctDNA is an unfavorable prognostic biomarker. Full article

Tacrolimus and mycophenolate are important immunosuppressive agents used to prevent organ rejection in post-transplant patients. While highly effective, their use is associated with significant toxicity, requiring careful management. Tacrolimus, a calcineurin inhibitor, is linked to nephrotoxicity, neurotoxicity, metabolic disturbances such as diabetes mellitus and dyslipidemia, and cardiovascular complications such as hypertension and arrhythmias. Mycophenolate, a reversible inhibitor of inosine monophosphate dehydrogenase, frequently causes gastrointestinal disturbances, including diarrhea and colitis, as well as hematologic side effects like anemia and leukopenia, which increase infection risk. Therapeutic drug monitoring (TDM) and pharmacogenomics have emerged as essential strategies for mitigating these toxicities. TDM ensures tacrolimus trough levels are maintained within a therapeutic range, minimizing the risks of nephrotoxicity and rejection. Pharmacogenomic insights, such as CYP3A5 polymorphisms, allow for personalized tacrolimus dosing based on individual metabolic profiles. For mycophenolate, monitoring inosine monophosphate dehydrogenase activity provides a pharmacodynamic approach to dose optimization, reducing gastrointestinal and hematologic toxicities. Emerging tools, including dried blood spot sampling and pharmacokinetic modeling, offer innovative methods to simplify monitoring and enhance precision in outpatient settings. Despite their utility, the toxicity profiles of these drugs, including those of early immunosuppressants such as cyclosporine and azathioprine, necessitate further consideration of alternative immunosuppressants like sirolimus, everolimus, and belatacept. Although promising, these newer agents require careful patient selection and further research. Future directions in immunosuppressive therapy include integrating individual pharmacogenetic data to refine dosing, minimize side effects, and improve long-term graft outcomes. This narrative review underscores the importance of personalized medicine and advanced monitoring in optimizing post-transplant care. Full article

In recent years, the frequency and intensity of extreme temperature events have escalated, posing unprecedented challenges to ecosystems, economies, and human health. As global temperatures rise, these events are emerging as critical threats; therefore, understanding their changes is essential for developing strategies to mitigate their growing risks under global warming. In this study, we used ETCCDI (Expert Team on Climate Change Detection, Monitoring, and Indices) temperature indices to analyze future changes in extreme temperature events in the South Saskatchewan River Watershed (SSRW) in Southern Alberta, Canada, a critical area for irrigation, agriculture, and food production. This analysis is based on an ensemble of 26 Global Circulation Models (GCMs) and three Shared Socio-economic Pathway (SSP) scenarios, in three periods (2015–2030, 2041–2060, 2071–2100), compared against the base period of 1951–1990. The results suggest substantial changes in most of the studied indices towards higher temperatures, with a significant rise in both the numbers of days with extreme temperatures and the magnitude of the temperature itself, as well as a notable drop in the number of cold days. As a result of warming, the growing season length is 16 days longer in 2015–2030 compared to the base period and is projected to increase substantially by the end of the century. A longer growing season might seem favourable for agriculture, but it can disrupt water availability and cause unpleasant environmental consequences. Overall, the scenarios considered in this research suggest that the SSRW could experience warming at a significant rate. This finding underscores the urgent need for adaptation and mitigation actions to enhance resilience and sustainability. Full article

In this study, a CMIP6 ensemble of 26 GCMs and SSP1-2.6, SSP2-4.5, and SSP5-8.5 scenarios from CanDCS-U6 is used to project drought conditions in the South Saskatchewan River Watershed. The near-current period (2015–2030) and two future periods (2041–2060 and 2071–2100) are analyzed based on the Standardized Precipitation Evapotranspiration Index (SPEI) at 1-, 3-, 6-, 12-, and 24-month timescales. Projections indicate a shift in average SPEI values from above zero (no drought) in the base period (1951–1990) to more negative values in the future. Results show an increase in drought severity and frequency under climate change conditions. The percentage of time with no drought conditions is projected to decline from 55–70% in the base period to 25–45% by 2071–2100. Severe and extreme droughts, rare in the base period (below 4%), are projected to increase to up to 19% by 2071–2100. The area experiencing drought is expected to expand from 36–49% (for different SPEI timescales) in the base period to up to 76% by 2071–2100. Drought frequency is projected to be higher under SSP1-2.6 and less frequent under SSP2-4.5. Results showed that longer SPEI timescales are associated with higher drought occurrence rates and severity. The spatial pattern of drought is also projected to significantly change, with higher frequencies expected in the eastern parts of the watershed under climate change. Full article

A cross-disciplinary rapid scoping review was carried out, generally following the PRISMA-SCR protocol to examine historical racial and caste-based discrimination as structural determinants of health disparities in the 21st century. We selected 48 peer-reviewed full-text articles available from the University of Memphis Libraries database search, focusing on three selected case-study countries: the United States (US), Canada, and Nepal. The authors read each article, extracted highlights, and tabulated the thematic contents on structural health disparities attributed to racism or casteism. The results link historical racism/casteism to health disparities occurring in Black and African American, Native American, and other ethnic groups in the US; in Indigenous peoples and other visible minorities in Canada; and in the Dalits of Nepal, a population racialized by caste, grounded on at least four foundational theories explaining structural determinants of health disparities. The evidence from the literature indicates that genetic variations and biological differences (e.g., disease prevalence) occur within and between races/castes for various reasons (e.g., random gene mutations, geographic isolation, and endogamy). However, historical races/castes as socio-cultural constructs have no inherently exclusive basis of biological differences. Disregarding genetic discrimination based on pseudo-scientific theories, genetic testing is a valuable scientific means to achieve the better health of the populations. Epigenetic changes (e.g., weathering—the early aging of racialized women) due to the DNA methylation of genes among racialized populations are markers of intergenerational trauma due to racial/caste discrimination. Likewise, chronic stresses resulting from intergenerational racial/caste discrimination cause an “allostatic load”, characterized by an imbalance of neuronal and hormonal dysfunction, leading to occurrences of chronic diseases (e.g., hypertension, diabetes, and mental health) at disproportionate rates among racialized populations. Major areas identified for reparative policy changes and interventions for eliminating the health impacts of racism/casteism include areas of issues on health disparity research, organizational structures, programs and processes, racial justice in population health, cultural trauma, equitable healthcare system, and genetic discrimination. Full article

The reduction in the blood supply following the 2019 coronavirus pandemic has been exacerbated by the increased use of balanced resuscitation with blood components including whole blood in urban trauma centers. This reduction of the blood supply has diminished the ability of blood banks to maintain a constant supply to meet the demands associated with periodic surges of urban trauma resuscitation. This scarcity has highlighted the need for increased vigilance through blood product stewardship, particularly among severely bleeding trauma patients (SBTPs). This stewardship can be enhanced by the identification of reliable clinical and laboratory parameters which accurately indicate when massive transfusion is futile. Consequently, there has been a recent attempt to develop scoring systems in the prehospital and emergency department settings which include clinical, laboratory, and physiologic parameters and blood products per hour transfused as predictors of futile resuscitation. Defining futility in SBTPs, however, remains unclear, and there is only nascent literature which defines those criteria which reliably predict futility in SBTPs. The purpose of this review is to provide a focused examination of the literature in order to define reliable parameters of futility in SBTPs. The knowledge of these reliable parameters of futility may help define a foundation for drawing conclusions which will provide a clear roadmap for traumatologists when confronted with SBTPs who are candidates for the declaration of futility. Therefore, we systematically reviewed the literature regarding the definition of futile resuscitation for patients with trauma-induced hemorrhagic shock, and we propose a concise roadmap for clinicians to help them use well-defined clinical, laboratory, and viscoelastic parameters which can define futility. Full article

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15–90. The effects of dementia, mild cognitive impairment, Parkinson’s disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders. Full article

Although there have been some advances during in recent decades, the treatment of head and neck squamous cell carcinoma (HNSCC) remains challenging. Resistance is a major issue for various treatments that are used, including both the conventional standards of care (radiotherapy and platinum-based chemotherapy) and the newer EGFR and checkpoint inhibitors. In fact, all the non-surgical treatments currently used for HNSCC are associated with intrinsic and/or acquired resistance. Herein, we explore the cellular mechanisms of resistance reported in HNSCC, including those related to epigenetic factors, DNA repair defects, and several signaling pathways. This article discusses these mechanisms and possible approaches that can be used to target different pathways to sensitize HNSCC to the existing treatments, obtain better responses to new agents, and ultimately improve the patient outcomes. Full article

Background: Given the aging of the overall U.S. population, the resulting changes in healthcare needs especially among veterans, and the high prevalence of traumatic brain injury (TBI) among older adults, additional research is needed on community participation after TBI in older veterans. The current study examined predictors of community participation trajectories over the 5 years after TBI in veterans who were 55 years of age or older upon injury. Method: This study included data from 185 participants in the U.S. Department of Veterans Affairs TBI Model System national study who had sustained a TBI at age 55 or older and had completed at least one of each Participation Assessment with Recombined Tools-Objective (PART-O) subscale scores at one or more follow-up time points (1, 2, and 5 years post-TBI). Results: PART-O Productivity, Social, and Out and About scores remained constant over time. Lower PART-O Productivity trajectories were seen among participants who were unemployed at the time of injury (p = 0.023). Lower PART-O Social trajectories were seen among participants who had a lower education level (p = 0.021), were unmarried at injury (p < 0.001), and had private insurance coverage (p < 0.033). Conclusion: These findings add to the growing body of literature on TBI and community participation by focusing on an older adult veteran population. There is an urgency to understand the needs of this group, many of whom are aging with service-connected disabilities including TBI. Veterans with characteristics identified herein as being associated with lower community participation trajectories would be prime candidates for interventions that aim to increase community and social engagement after later-life TBI. Full article

(1) Smoking is the most significant preventable health hazard in the modern world. It increases the risk of vascular problems, which are also risk factors for dementia. In addition, toxins in cigarettes increase oxidative stress and inflammation, which have both been linked to the development of Alzheimer’s disease and related dementias (ADRD). This study identified potential mechanisms of the smoking–cognitive function relationship using metabolomics data from the longitudinal Wisconsin Registry for Alzheimer’s Prevention (WRAP). (2) 1266 WRAP participants were included to assess the association between smoking status and four cognitive composite scores. Next, untargeted metabolomic data were used to assess the relationships between smoking and metabolites. Metabolites significantly associated with smoking were then tested for association with cognitive composite scores. Total effect models and mediation models were used to explore the role of metabolites in smoking-cognitive function pathways. (3) Plasma N-acetylneuraminate was associated with smoking status Preclinical Alzheimer Cognitive Composite 3 (PACC3) and Immediate Learning (IMM). N-acetylneuraminate mediated 12% of the smoking-PACC3 relationship and 13% of the smoking-IMM relationship. (4) These findings provide links between previous studies that can enhance our understanding of potential biological pathways between smoking and cognitive function. Full article

We describe the process to design, architect, and implement a transformative enhancement of the Event Horizon Telescope (EHT). This program—the next-generation Event Horizon Telescope (ngEHT)—will form a networked global array of radio dishes capable of making high-fidelity real-time movies of supermassive black holes (SMBH) and their emanating jets. This builds upon the EHT principally by deploying additional modest-diameter dishes to optimized geographic locations to enhance the current global mm/submm wavelength Very Long Baseline Interferometric (VLBI) array, which has, to date, utilized mostly pre-existing radio telescopes. The ngEHT program further focuses on observing at three frequencies simultaneously for increased sensitivity and Fourier spatial frequency coverage. Here, the concept, science goals, design considerations, station siting, and instrument prototyping are discussed, and a preliminary reference array to be implemented in phases is described. Full article

Extracellular vesicles (EVs) contribute to osteoarthritis pathogenesis through their release into joint tissues and synovial fluid. Synovial fluid-derived EVs have the potential to be direct biomarkers in the causal pathway of disease but also enable understanding of their role in disease progression. Utilizing a temporal model of osteoarthritis, we defined the changes in matched synovial fluid and plasma-derived EV small non-coding RNA and protein cargo using sequencing and mass spectrometry. Data exploration included time series clustering, factor analysis and gene enrichment interrogation. Chondrocyte signalling was analysed using luciferase-based transcription factor activity assays. EV protein cargo appears to be more important during osteoarthritis progression than small non-coding RNAs. Cluster analysis revealed plasma-EVs represented a time-dependent response to osteoarthritis induction associated with supramolecular complexes. Clusters for synovial fluid-derived EVs were associated with initial osteoarthritis response and represented immune/inflammatory pathways. Factor analysis for plasma-derived EVs correlated with day post-induction and were primarily composed of proteins modulating lipid metabolism. Synovial fluid-derived EVs factors represented intermediate filament and supramolecular complexes reflecting tissue repair. There was a significant interaction between time and osteoarthritis for CRE, NFkB, SRE, SRF with a trend for osteoarthritis synovial fluid-derived EVs at later time points to have a more pronounced effect. Full article