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Caspase-4 has potential utility as a colorectal tissue biomarker for dysplasia and early-stage cancer
No full textBackground and aimsColorectal cancer (CRC) is the second most deadly cancer globally. The rapidly rising incidence rate of CRC, coupled with increased diagnoses in individuals MethodsTissue samples from patients with CRC, colonic polyps, IBD-CRC, and sCRC were assessed by immunohistochemistry for caspase-4 expression in epithelial and stromal compartments. RNAseq expression data for caspase-4 in CRC and normal tissue samples were mined from online databases.ResultsEpithelial caspase-4 expression is selectively elevated in CRC tumor tissue compared to adjacent normal tissue, where it is not expressed. In the sCRC pathway, caspase-4 is expressed in the epithelial and stromal tissue of all histological subtypes of colonic polyps, with a significant increase in epithelial expression from low-grade dysplasia to high-grade dysplasia progression. For the IBD-CRC pathway, caspase-4 epithelial expression was specifically upregulated in dysplastic and neoplastic tissue of IBD-CRC but was not expressed in normal or inflamed tissue.ConclusionThis study demonstrates that epithelial caspase-4 is selectively expressed in colon tissue during the development of dysplasia. As such, epithelial caspase-4 represents a promising novel tissue biomarker for CRC risk and diagnosis
Assessing the performance of diffusive gradients in thin films for plant available phosphorus in northern Irish dairy farms
No full textPhosphorus (P) loss from agricultural land is contributing to the enrichment of surface waterbodies and is a reason why water quality in Northern Ireland (NI) is failing to meet Water Framework Directive targets. In NI the agronomic and environmental targets for soil P are based on measurements of sodium bicarbonate extractable-P (Olsen P), however, this methodology has been shown to underestimate bioavailable P in the iron and aluminium rich basalt derived soils of the Antrim Plateau, which covers approximately one third (450 km2) of the land area of NI. In our study an alternative advanced speciation method, namely Diffusive Gradients in Thin films (DGT), was used to assess P bioavailability on dairy farm soils in NI and compared it with traditional soil extractions used on the island of Ireland (Olsen P (in NI) and Morgan's P (in the Republic of Ireland). We observed variability in P status depending on soil test P (STP) method used (Olsen P, Morgan's P or DGT). DGT was the only STP method to significantly correlate with Herbage P and had a significant linear relationship with Herbage P in soil from Basalt regions (R2 = 0.62). We found DGT to be a better predictor of the plant available P pool in soil in Northern Irish Dairy farms and recommend that DGT be incorporated into more extensive field trials and national/multi-national surveys
Implantable rectal spacers (IRS) in prostate cancer radiotherapy: a systematic review
No full textPurposeThis systematic review provides an overview of the available literature regarding the efficacy and safety of implantable rectal spacers (IRSs) in reducing rectal dose and gastrointestinal toxicity during prostate cancer radiation therapy.Methods and MaterialsA comprehensive literature search was conducted in December 2024. Results included prospective research in humans and were limited to the English language. The 30 included studies, all published between 2007 and 2024, were randomized controlled trials or clinical trials that focused on adverse events, rectal dose reduction, gastrointestinal toxicity, or bowel quality of life. Next, IRS implantation technique, safety, and spacing distance were assessed.ResultsRandomized controlled trial data were available for hydrogel, hyaluronic acid, and rectal balloon implant spacers, whereas only one pilot study is available for human collagen. Prospective clinical research on IRS in brachytherapy is limited. One centimeter of spacing between the rectum and prostate sufficed to spare the rectum, the primary dose-limiting organ. Findings indicate a favorable safety profile, with an overall complication rate of 0,96% when using hydrogel spacers. There was no grade 4 to 5 gastrointestinal toxicity reported in clinical trials. The use of an IRS was associated with improved long-term bowel quality of life.ConclusionsThe integration of IRS into clinical practice offers the potential to enhance the therapeutic landscape for patients with prostate cancer. However, its use should be guided by careful consideration of individual patient needs to determine those who benefit most from the IRS because not all patients may benefit equally
Microstructure, porosity, and bending fatigue behaviour of PBF-LB/M SS316L for biomedical applications
No full textBending fatigue significantly affects the mechanical stability and lifespan of biomedical implants, such as bone plates and orthopaedic fixation devices, which undergo cyclic loading in the human body. This study examines the microstructure, porosity, and bending fatigue properties of PBF-LB/M SS316L. Samples were analysed across three faces (top, front, and side) using optical microscopy (OM) and scanning electron microscopy (SEM) to observe microstructural features and porosity. Elemental composition was measured by energy-dispersive X-ray spectroscopy (EDX). Phase structures and grain orientations were characterised via X-ray diffraction (XRD) and electron backscatter diffraction (EBSD). Four-point bending fatigue tests, conducted under two loading conditions, below and slightly above the yield point, demonstrated that defects inherent to the PBF-LB/M process, particularly micropores and unmelted powder particles, strongly influence fatigue crack initiation. Real-time monitoring of crack initiation and propagation on the external sample surface was performed using a high-speed digital microscope. These findings indicate the influence of microstructural defects on fatigue performance in PBF-LB/M SS316L, supporting the design and development of more reliable patient-specific biomedical implants
NGTS-EB-8: a double-lined eclipsing M+M binary discovered by citizen scientists
No full textWe report the identification and characterization of a new binary system composed of two near-equal mass M-dwarfs. The binary NGTS-EB-8 was identified as a planet candidate in data from the Next Generation Transit Survey (NGTS) by citizen scientists participating in the Planet Hunters NGTS project. High-resolution spectroscopic observations reveal the system to be a double-lined binary. By modeling the photometric and radial velocity observations, we determine an orbital period of 4.2 days and the masses and radii of both stars to be MA=0.250+0.005−0.004 M⊙, MB=0.208+0.005−0.004 M⊙, and RA=0.255+0.004−0.005 R⊙, RB=0.233+0.006−0.005 R⊙, respectively. We detect Balmer line emission from at least one of the stars but no significant flare activity. We note that both components lie in the fully convective regime of low-mass stars (≲0.35 M⊙); therefore, they can be a valuable test for stellar evolutionary models. We demonstrate that the photometric observations, speckle imaging, and initial radial velocity measurements were unable to identify the true nature of this system and highlight that high-resolution spectroscopic observations are crucial in determining whether systems such as this are in fact binaries.<br/
Fire activity in the northern Arctic tundra now exceeds late Holocene levels, driven by increasing dryness and shrub expansion
No full textTundra ecosystems are characterized by small, rare and infrequent fires due to cold, often waterlogged conditions, and limited biomass. However, ongoing climate warming and drying in northern soils and peatlands are contributing to increasingly frequent and extensive wildfires. To place recent fire regimes in the context of long-term variability and to better understand interactions between fire, moisture, and vegetation, we reconstructed wildfire history over the past 3000 years using a network of charcoal, vegetation, and hydrological records in combination with satellite-derived fire datasets from northern Arctic Alaska peatlands. The composite charcoal record shows minimal fire activity from ĝ1/4 1000 BCE to 1000 CE, followed by a modest increase between 1000 and 1200 CE, and then a renewed decline. This long-term pattern shifted abruptly after 1900 CE, reaching its maximum between 1950 and 2015 CE, when fire activity exceeded any levels observed in the preceding three millennia. Individual charcoal records show a spatially heterogeneous pattern in fire occurrence before 1950 CE, and a more homogeneous one thereafter. Our findings suggest that the deepening of water tables and peatland drying associated with permafrost thaw have facilitated woody encroachment, especially by more flammable Ericaceous shrubs. These vegetation changes have increased fuel availability and flammability, ultimately driving the recent surge in wildfire activity, highlighting the growing vulnerability of Arctic tundra ecosystems to fire. We also found that the charcoal source area of our tundra fire reconstruction encompasses broader landscapes over tens of kilometres. Our study emphasizes the significance of long-term, multidisciplinary research in documenting moisture-vegetation-fire feedbacks that influence tundra fire regimes. Ultimately, this long-term fire dynamic study provides critical context for evaluating recent changes and incorporating tundra peatland fire risk into global climate mitigation strategies.</p
Semi-submersible hybrid platforms for wind–wave hydrodynamic performance: high-fidelity numerical simulations powered by SPH
No full textHybrid wave–wind energy platforms seem a promising way forward to elevate renewable energy power production by blending in wave energy converters (WEC) and wind turbines. This work proposes an extreme performance estimation through high-fidelity software for a power unitcomprising a 5-MW NREL wind turbine and three WaveStar devices using a numerical framework based on DualSPHysics, which implements the Smoothed Particle Hydrodynamics method to solve the fluid dynamics, powered by state-of-the-art GPU parallelization. First, we validate the response of the power unit by relying on sub-component model validations, specifically, validating an OC4 DeepCwind layout under operational frequencies, and, using their spectral representation, we compare the hybrid platform performance during power production. Using incremental sea-states, we employ the model to evaluate the platform-to-WEC sensitivity for two cases: no power absorption and operational, respectively. This investigation shows that the platform heave and pitch motion increase by about two and three times, respectively, when the devices are operating at their optimal damping. On the other hand, the surge motion only increases by around 50%. It is clear – combined wave and wind energy platforms are more susceptible to wave induced loads when the wave energy process is not interrupted, suggesting how WECs combined to FOWTs do not generally provide a stabilizing effect unless more specific strategies are enforced
Proteome atlas for mechanistic discovery and risk prediction of diabetic retinopathy
No full textProteomics offers an unprecedented opportunity to characterize and predict diabetic retinopathy (DR) with minimal invasiveness. Here we examine this in 10,873 individuals with (pre)diabetes from two ethnically distinct cohorts. By simultaneous profiling of ~3000 proteins, we identify 668 associations with mechanistically plausible directionality that constitute a comprehensive DR proteomic landscape with linkages to retinal tomographic structure and genetic predisposition, pointing to established and novel biological pathways conferring DR risk. Integrating DR proteomic profile markedly improves predictive performance beyond clinical and genetic predictors, with plexin B2, growth differentiation factor 15, and renin emerging as top proteins validated across cohorts and linked to retinal microvascular degeneration in Guangzhou Diabetic Eye Study (GDES) based on SS-OCTA. A parsimonious panel of these three proteins alone achieves comparable performance in predicting DR development and progression, while renin is confirmed as a causal promoter through genetic analyses. Our findings highlight the potential of large-scale proteomics in elucidating DR pathogenesis and advancing biomarker discovery, with broad implications for early detection and intervention
Projected hospitalization cost impact of the selective cytopheretic device in pediatric acute kidney injury
No full textThe Selective Cytopheretic Device for Pediatrics (SCD-PED) is a cell-directed extracorporeal therapy approved by the Food and Drug Administration through the humanitarian device exemption pathway for patients≥10kg, age≤22 years with acute kidney injury due to sepsis or a septic condition requiring antibiotics and on continuous renal replacement therapy (CRRT). We leveraged the Kids' Inpatient Database (KID) and SCD-PED study data to estimate hospitalization costs with and without SCD-PED therapy. A cost regression model was built from KID hospitalizations (2019) that included patients aged 1-20 years with AKI receiving CRRT, total parenteral nutrition, KID mortality risk=4, KID severity=4, and hospital length of stay (LOS) ≤60 days. Data assessed as cost predictors included patient age, sex, vasopressor use, mechanical ventilation, sepsis, theoretical SCD-PED cost/number used, LOS, and death at hospital discharge. Differences in mean costs between a matched control cohort from the Prospective Pediatric CRRT registry (ppCRRT) and the SCD-PED study cohort were estimated from the model using SCD-PED study mortality rates and LOS reported in the SCD-PED studies. Modeled hospitalization costs were 389,451 in ppCRRT ( = 210). Median hospital LOS was lower in the SCD-PED group ( = 22): 28 days vs. 31 days in the control group, which despite the lower mortality rate, resulted in a lower estimated cost of 69,146 per hospitalization. The model in the current study compares patients using SCD-PED to an external control cohort with similar characteristics, because controls were not examined in the original clinical studies. This study is not intended to be predictive of costs in other patient types or larger populations. Additional study is needed. The SCD-PED is likely cost-beneficial in critically ill children with AKI requiring CRRT, including those with sepsis