Search Results (36)

Background: Breast cancer polygenic risk scores (PRS) and traditional risk models (e.g., the Gail model [Gail]) are known to contribute largely independent information, but it is unclear how the overlap varies by ancestry, age, disease type (invasive breast cancer, DCIS), and risk threshold. Methods: In a retrospective case–control study, we evaluated risk prediction performance in 180,398 women (161,849 of European ancestry; 18,549 of Asian ancestry). Odds ratios (ORs) from logistic regression models and the area under the receiver operating characteristic curve (AUC) were estimated. Results: PRS for invasive disease showed a stronger association in younger (<50 years) women (OR = 2.51, AUC = 0.622) than in women ≥ 50 years (OR = 2.06, AUC = 0.653) of European ancestry. PRS performance in Asians was lower (OR range = 1.62–1.64, AUC = 0.551–0.600). Gail performance was modest across groups and poor in younger Asian women (OR = 0.94–0.99, AUC = 0.523–0.533). Age interactions were observed for both PRS (p < 0.001) and Gail (p < 0.001) in Europeans, whereas in Asians, age interaction was observed only for Gail (invasive: p < 0.001; DCIS: p = 0.002). PRS identified more high-risk individuals than Gail in Asian populations, especially ≥50 years, while Gail identified more in Europeans. Overlap between PRS, Gail, and family history was limited at higher thresholds. Calibration analysis, comparing empirical and model-based ROC curves, showed divergence for both PRS and Gail (p < 0.001), which indicates miscalibration. In Europeans, family history and prior biopsies drove Gail discrimination. In younger Asians, age at first live birth was influential. Conclusions: PRS adds value to risk stratification beyond traditional tools, especially in younger women and Asian ancestry populations. Full article

This study was conducted in two phases: first, to assess the impact of microbial fermentation on enhancing the nutritional quality of fish by-products, and second, to evaluate the effects of replacing fishmeal with these fermented by-products in the diet of Nile tilapia (Oreochromis niloticus) on growth performance, blood parameters, antioxidant indices, immunity, digestive enzyme activity, and carcass composition. In the initial phase, proteolytic activity of five bacterial strains including Bacillus subtilis (ATCC: 6051), B. licheniformis (IBRCM: 10204), Lactiplantibacillus plantarum (PTCCs: 1058 and 1745), and Lactobacillus casei (PTCC: 1608) was evaluated using growth assays in skimmed milk culture media and analyzed using Image-J software. B. licheniformis exhibited the highest proteolytic activity and was selected for fermentation. Resulting hydrolyzed proteins were characterized by peptides with molecular weights below 11 kDa. In the second phase, fishmeal was replaced with fermented by-products at five levels (0 (control), 25, 50, 75, and 100%). Two hundred ten Nile tilapia with an average weight of 2.83 ± 0.05 g were stocked in fifteen 200 L plastic tanks at three replicates, with 14 fish per tank, and fed daily at a rate of 7% of their body weight for 63 days. With increasing levels of fishmeal replacement (25% to 75%), significant improvements (p < 0.05) were observed in final weight gain, body weight gain, specific growth rate, protein production value, and protein efficiency ratio. Additionally, blood plasma concentrations of hormones T₃ and T₄, immunoglobulin level, the activities of complement (ACH₅₀), and antioxidant enzymes (catalase and superoxide dismutase) increased significantly in fish fed the diets with fermented by-products compared to those of the control diet (p < 0.05). The optimal replacement levels for specific growth rate and feed conversion ratio were identified as 86.28% and 83.91%, respectively. Full article

Proton pump inhibitors (PPIs) are among the most prescribed drugs worldwide owing to their proven efficacy in symptom control and mucosal healing for acid-related disorders including gastroesophageal reflux disease (GORD), peptic ulcer disease, Helicobacter pylori eradication, functional dyspepsia, and gastroprotection in high-risk patients. However, long-term use beyond approved indications is increasingly common and has raised safety concerns. Observational studies link chronic PPI use to a myriad of adverse outcomes such as enteric infections (e.g., Clostridioides difficile), nutrient deficiencies (magnesium, vitamin B12), osteoporotic fractures, chronic kidney disease, dementia, and gastric and colorectal cancer. While causality is not always established, these associations warrant cautious risk–benefit assessment in patients receiving prolonged therapy. Current guidelines advocate periodic review of ongoing PPI use and emphasise deprescribing where appropriate. Strategies include dose reduction, on-demand or intermittent use, and switching to H2-receptor antagonists, particularly in patients with non-erosive reflux disease or functional dyspepsia. Tools from the National Institute for Health and Clinical Excellence, American College of Gastroenterology, and the Canadian Deprescribing Network assist clinicians in identifying candidates for tapering or discontinuation. This narrative review focuses on the concept of “PPI stewardship” by providing an evidence-based overview of PPI indications, risks, and deprescribing strategies to promote appropriate, safer, and patient-centred use of acid-suppressive therapy. Full article

This study seeks to develop and evaluate a methodological framework for assessing the tourism potential of hillforts, by using a selected sample of 25 of these heritage resources located in the Lower Silesia Voivodeship. This region, as one of Poland’s most popular among domestic and international tourists, is increasingly confronting overtourism at its primary attractions. Concurrently, it possesses underutilised cultural assets, notably 250 remnants of gords/hillforts (grodziska in Polish) spanning various historical periods and dispersed across the whole area. Thus, to ensure the universality of the method, samples of hillforts from three main topographic zones of Lower Silesia were selected. In addition to the aim of testing the method, a secondary objective of the research involved conducting a preliminary assessment of selected hillforts’ tourism potential in different parts of the voivodeship. The methodology combined desk research and field studies across all selected archaeological sites. Concerning the primary objective, the developed assessment tool effectively replicated the multidimensional analytical framework characteristic of established methodologies, yielding reliable outcomes for evaluating gords’ tourism potential. However, modifications to the scoring system are recommended to enhance methodological precision. Regarding analysis of the 25 surveyed hillforts, the results indicate that objects from all zones mainly demonstrate high tourism potential, suggesting an opportunity for transformation into tourist attractions. The integration of hillforts into existing tourism infrastructure could significantly contribute to localised sustainable development across the region. The primary significance of these heritage resources lies in their capacity to facilitate the diversification of tourism offerings across distinct areas of the voivodeship. This development holds particular strategic value for northern poviats currently peripherally engaged in tourism economy. Moreover, by leveraging hillforts, communities obtain assets important in the process of building a common identity around cultural/historical place while safeguarding monuments. Concurrently, the most attractive southern poviats will benefit from the new attractions as they can help in mitigating overtourism pressures at overcrowded places, being an interesting alternative to the top attractions. This approach aligns with strategies to disperse tourist flows through specialised archaeological tourism products, thereby balancing economic benefits and local communities’ well-being with heritage preservation. Full article

Wetlands, as critical ecological systems, face increasing threats from anthropogenic pressures and climate change. This study investigates dynamic water allocation strategies for the restoration of Lake Marmara, a nationally important wetland within the Gediz River Basin of Türkiye, which has experienced complete desiccation in recent years. Within the scope of the PRIMA-funded “Mara-Mediterra” project, an integrated modeling approach was employed to evaluate multiple restoration scenarios using the WEAP (Water Evaluation and Planning) platform. Scenarios varied based on the initial storage capacity of Gördes Dam, irrigation demands, environmental flow priorities, and a potential water diversion investment from the Tabaklı reach. Results indicate that under current conditions, Lake Marmara’s ecological water needs can be sustained without the Tabaklı investment. However, under 2050 climate projections, scenarios lacking the Tabaklı investment or deprioritizing ecological needs consistently failed to meet the lake’s minimum water thresholds. Conversely, scenarios combining moderate dam storage levels, environmental prioritization, and Tabaklı inflow succeeded in restoring lake volumes by over 90%. These findings highlight the need for adaptive water planning that aligns with projected hydro-climatic shifts to ensure long-term wetland sustainability. Full article

Amine transaminases (ATA) are critical players in producing non-canonical amino acids, essential building blocks in pharmaceuticals and fine chemicals. Significant progress has been made in discovering and engineering enzymes in this field, enhancing their use in organic synthesis. However, challenges such as co-factor regeneration, substrate, and product inhibition remain significant limitations to widespread industrial enzyme application. (Chemo-)enzymatic cascades offer efficient and environmentally friendly pathways for synthesizing amino acids, reducing the need for multiple synthesis steps and saving the purification of intermediates. This review focuses specifically on the synthesis of non-canonical amino acids, emphasizing the use of enzymatic and chemoenzymatic cascades involving ATA. Full article

High-pressure air injection (HPAI) is an enhanced oil recovery process in which compressed air is injected into deep, light oil reservoirs, with the expectation that the oxygen in the injected air will react with a fraction of the reservoir oil at an elevated temperature to produce carbon dioxide. The different chemical reactions taking place can be grouped into oxygen addition, thermal cracking, oxygen-induced cracking, and bond scission reactions. The latter reactions involve the combustion of a flammable vapor as well as the combustion of solid fuel, commonly known as “coke”. Since stable peak temperatures observed during HPAI experiments are typically below 300 °C, it has been suggested that thermal cracking and combustion of solid fuel may not be important reaction mechanisms for the process. The objective of this work is to assess the validity of that hypothesis. Therefore, this study makes use of different oxidation and combustion HPAI experiments, which were performed on two different light oil reservoir samples. Modeling of those tests indicate that thermal cracking is not an important reaction mechanism during HPAI and can potentially be ignored. The work also suggests that the main fuel consumed by the process is a flammable vapor generated by the chemical reactions. This represents a shift from the original in situ combustion paradigm, which is based on the combustion of coke. Full article

Introduction: The upper gastrointestinal microbiome is a dynamic entity that is involved in numerous processes including digestion, production of vitamins and protection against pathogens. Many external and intrinsic factors may cause changes in the proportions of bacteria within the microbial community, termed ‘dysbiosis’. A number of these have been identified as risk factors for a range of diseases, including oesophago-gastric carcinoma. Materials and Methods: A narrative review was conducted to elucidate the current evidence on the role of the microbiome in promoting oesophago-gastric tumourigenesis. Significant causes of dysbiosis including age, medications and GORD were examined and key pro-inflammatory pathways implicated in tumourigenesis and their interaction with the microbiome were described. Results and Discussion: An association between microbial dysbiosis and development of oesophago-gastric cancer may be mediated via activation of pro-inflammatory pathways, the inflammasome and the innate immune system. Advances in sequencing technology allow microbial communities to be fingerprinted by sequencing the 16S rRNA gene, enabling a deeper understanding of the genera that may be implicated in driving tumourigenesis. Conclusions: Developing a greater understanding of the influence of the microbiota on oesophago-gastric tumourigenesis may enable advances to be made in the early detection of malignancy and in the development of novel systemic therapies, leading to improved rates of survival. Full article

Background/Objectives: Gastroesophageal reflux disease (GORD) is caused by gastric contents refluxing back into the oesophagus and oral cavity. It can lead to injuries to the mucosa in the form of erosion and ulcers. Our past research have shown acid reflux severity and disease progression is associated with alternations in the microbiota of the distal oesophagus. The aim of this study was to explore whether changes in the oral microbiota occurred in GORD patients and establish any associations with reflux severity. Methods: Fresh mouthwash samples were collected from 58 patients experiencing reflux symptoms referred for 24 h pH monitoring. The participants were categorised into three groups based on their DeMeester scores: Normal (<14.72), Mild (14.2–50), and Moderate/severe (>51). Microorganism identity and diversity were generated using hypervariable tag sequencing and analysing the V1–V3 region of the 16S rRNA gene. Results: No differences in microbiota diversity were found in oral microbiota between groups using the Chiao1 diversity index and Shannon diversity index. Microbiota in the Mild group showed reductions in Rothia dentocariosa and Lautropia, while Moryella and Clostridiales_1 were increased compared with the Normal group. In the Moderate/severe group, the abundance of Rothia aeria was reduced compared with the Normal group, while Schwartzia, Rs_045, Paludibacter, S. satelles, Treponema, and T. socranskii all had increased abundance. The abundance of Prevotella pallens was higher in the Mild group compared with Moderate/severe, while S. satelles and Paludibacter abundances were lower. Conclusions: Our study shows the oral microbiome show significant differences between acid reflux severity groups, as categorised by DeMeester score. Full article

The aim of this in vivo study was to compare total protein present in the salivary films (F) and acquired enamel pellicle (AEP) on eroded and non-eroded surfaces in patients suffering from GORD symptoms with and without GORD diagnosis (GORD, No-GORD). Thirty-nine patients suffering from GORD symptoms and erosive tooth wear on lower first molars and an unaffected posterior occlusal surface in the same quadrant were recruited from Guy’s hospital, London. Salivary film and AEP were collected from the eroded and uneroded occlusal surfaces, using 0.5% sodium dodecyl sulphate (SDS)-soaked filter papers. Total protein concentration was analysed using bicinchoninic acid assay (BCA). Statistical analysis was conducted using Shapiro–Wilk, ANOVA, and Tukey’s tests (p < 0.05), comparing four GDS sample types and GORD vs. No-GORD groups. The level of significance was set as p < 0.05. Data were compared between eroded and uneroded surfaces in the same patient with GORD symptoms, as well as between those with or without a GORD diagnosis (GORD, No-GORD). The AEP total protein concentration from the eroded [2.17 (0.49) mg/mL] and uneroded surfaces [2.24 (0.66) mg/mL] of the GORD group were statistically significantly lower than those on eroded [3.27 (1.01) mg/mL] and uneroded [3.33 (1.57) mg/mL] surfaces in the No-GORD group (p = 0.007) (p = 0.008), respectively. No statistically significant differences were observed for film and AEP between eroded and uneroded surfaces (p > 0.05). Full article

Population and tourism growth has increased congestion, collisions, climate harming emissions, and transport inequities in the Okanagan Valley, British Columbia (B.C.), Canada. Surveys indicate a willingness among residents to switch from cars to public transit featuring better service levels and connections. We conducted an analysis on the economic feasibility of an Okanagan Valley Electric Regional Passenger Rail (OVER PR) powered by zero-emission (ZE) Fuel Cell/Battery Hybrid Rail (Hydrail) technology along a 342-km route between Osoyoos, B.C., at the US Border and Kamloops, B.C., the Canadian VIA rail hub. Hydrail passenger light-rail has operated successfully since 2018 in Germany and was demonstrated in Quebec, Canada, in 2023. Technical analyses have confirmed the feasibility in B.C. on steep Highway (Hwy) 97 grades and mountainous weather, with mode shift forecasts in the range of 30%. OVER PR economic analyses were also favorable, with net present value (NPV) = CAD 40 billion (CDN, base year 2023), benefit–cost ratio (BCR) = 9:1, and Return on Investments (IRR) = 33% over 30 years. Subject to additional stakeholder consultations and final design reviews, these results were tested against risks using Monte Carlo Simulation (MCS) and Reference-Class Forecasting (RCF), including worst-case risks such as 70% cost over-runs. OVER PR promises an economic transition to clean energy, sustainable transportation, and more livable communities, benefiting all Valley communities through greater transportation equity. Full article

The Mediterranean region is highly vulnerable to climate change. Longer and more intense heatwaves and droughts are expected. The Gordes Dam in Turkey provides drinking water for Izmir city and irrigation water for a wide range of crops grown in the basin. Using the Soil and Water Assessment Tool (SWAT), this study examined the effects of projected climate change (RCP 4.5 and RCP 8.5) on the simulated streamflow, nitrogen loads, and crop yields in the basin for the period of 2031–2060. A hierarchical approach to define the hydrological response units (HRUs) of SWAT and the Fast Automatic Calibration Tool (FACT) were used to reduce computational time and improve model performance. The simulations showed that the average annual discharge into the reservoir is projected to increase by between 0.7 m³/s and 4 m³/s under RCP 4.5 and RCP 8.5 climate change scenarios. The steep slopes and changes in precipitation in the study area may lead to higher simulated streamflow. In addition, the rising temperatures predicted in the projections could lead to earlier spring snowmelt. This could also lead to increased streamflow. Projected nitrogen loads increased by between 8.8 and 25.1 t/year. The results for agricultural production were more variable. While the yields of poppy, tobacco, winter barley, and winter wheat will increase to some extent because of climate change, the yields of maize, cucumbers, and potatoes are all predicted to be negatively affected. Non-continuous and limited data on water quality and crop yields lead to uncertainties, so that the accuracy of the model is affected by these limitations and inconsistencies. However, the results of this study provide a basis for developing sustainable water and land management practices at the catchment scale in response to climate change. The changes in water quality and quantity and the ecological balance resulting from changes in land use and management patterns for economic benefit could not be fully demonstrated in this study. To explore the most appropriate management strategies for sustainable crop production, the SWAT model developed in this study should be further used in a multi-criteria land use optimization analysis that considers not only crop yields but also water quantity and quality targets. Full article

Booming population and tourism have increased congestion, collisions, climate-harming emissions, and transport inequities in The Okanagan Valley, Canada. Surveys suggest that over 30% of residents would shift from cars back to public transit and intercity tram–trains if regional service and connections were improved. Intercity streetcars (aka light-rail tram–trains) have not run in Canada since their replacement in the 1950′s by the national highway system. UBC researchers analyzed a tram–train service fashioned after the current Karlsruhe model but powered by zero-emission hydrogen fuel cell/battery hybrid rail power (hydrail) technology, along a 342 km route between Osoyoos, B.C. at the US Border and Kamloops, B.C., the Canadian VIA rail hub. Hydrail trains have operated successfully since 2018 in Germany and were demonstrated in Quebec, Canada in 2023. However, hydrail combined with tram–train technology has never been tried in Canada. Single-train simulations (STSs) confirmed its technical feasibility, showing a roughly 8 h roundtrip travel time, at an average train velocity of 86 km/h. Each hydrail tram–train consumed 2400 kWh of energy, translating to 144 kg of hydrogen fuel per roundtrip. In total, five tons of H₂/day would be consumed over 16 h daily by the 16-tram–train-vehicle fleet. The results provide valuable insights into technical aspects and energy requirements, serving as a foundation for future studies and decision-making processes in developing zero-emission passenger tram–train services not just for Okanagan Valley communities but all of Canada and NA. Full article

Ultrafiltration (UF) polymeric membranes are widely used in water treatment and support desalination and gas separation membranes. In this article, we enhance the performance of Polysulfone (PSF) mixed matrix membranes (MMMs) by dispersing different concentrations of thermally reduced graphene (TRG) nanofillers. The UF PSF-TRG MMMs were fabricated via the phase inversion process, and the impact of TRG loading on the characteristics of the membrane, including hydrophilicity, porosity, roughness, and morphology, were analyzed using a contact angle measurement, atomic force microscopy (AFM), scanning electron microscopy (SEM), and dynamic mechanical analysis. Incorporating TRG into the PSF matrix led to favorable effects in the instantaneous de-mixing during phase inversion, increasing the porosity and hydrophilicity of MMMs and improving the mechanical properties of the membranes. Moreover, membrane performance was examined to remove dispersed oil from oil–water emulsion and support air-dehumidification membranes. MMM performance in terms of flux and oil rejection was superior to the control PSF membrane. Incorporating 0.25% TRG into PSF resulted in a 70% water flux increase and higher oil rejection compared to the control PSF membrane. As a support for air-dehumidification membranes, the MMM also demonstrated enhanced humidity reduction and an over 20% increase in water vapor permeance over the control PSF membrane. These results indicate that the PSF-TRG MMMs are an excellent candidate for reliable oil–water separation and as a support for air-dehumidification membranes. Full article

Porous low-pressure membranes have been used as active membranes in water treatment and as support for thin-film composite membranes used in water desalination and gas separation applications. In this article, microfiltration polysulfone (PSf)mixed-matrix membranes (MMM) containing amine-functionalized graphene oxide (GO-NH₂) were fabricated via a phase inversion process and characterized using XPS, SEM, AFM, DMA, XRD, and contact angle measurements. The effect of GO-NH₂ concentration on membrane morphology, hydrophilicity, mechanical properties, and oil–water separation performance was analyzed. Significant enhancements in membrane hydrophilicity, porosity, mechanical properties, permeability, and selectivity were achieved at very low GO-NH₂ concentrations (0.05–0.2 wt.%). In particular, the water permeability of the membrane containing 0.2 wt.% GO-NH₂ was 92% higher than the pure PSf membrane, and the oil rejection reached 95.6% compared to 91.7% for the pure PSf membrane. The membrane stiffness was also increased by 98% compared to the pure PSf membrane. Importantly, the antifouling characteristics of the PSf-GO-NH₂ MMMs were significantly improved. When filtering 100 ppm bovine serum albumin (BSA) solution, the PSf-GO-NH₂ MMMs demonstrated a slower flux decline and an impressive flux recovery after washing. Notably, the control membrane showed a flux recovery of only 69%, while the membrane with 0.2 wt.% GO-NH₂ demonstrated an exceptional flux recovery of 88%. Furthermore, the membranes exhibited enhanced humidity removal performance, with a permeance increase from 13,710 to 16,408. These results indicate that the PSf-GO-NH₂ MMM is an excellent candidate for reliable oil–water separation and humidity control applications, with notable improvements in antifouling performance. Full article