Search Results (8,275)

Salinization of olive orchards constitutes a front-line agronomic challenge for farmers, consumers, and the scientific community as food security, olive logistics, and land use become more unsustainable and problematic. Plantlets of two olive varieties (var. Kalamon and var. Koroneiki) were tested for their performance under soil saline conditions, in which L-methionine, choline-Cl, and L-proline betaine were applied foliarly to alleviate adverse effects. The ‘Kalamon’ variety ameliorated its photosynthetic rates when L-proline betaine and L-methionine were administered at low saline exposure. The stressed varieties achieved higher leaf transpiration rates in the following treatment order: choline-Cl > L-methionine > L-proline betaine. Choline chloride supported stomatal conductance in stressed var. Kalamon olives without this pattern, which was also followed by var. Koroneiki. Supplementation regimes created a mosaic of responses on varietal water use efficiency under stress. The total phenolic content in leaves increased in both varieties after exogenous application only at the highest levels of saline stress. None of the substances applied to olive trees could stand alone as a tool to mitigate salinity stress in order to be recommended as a solid agronomic practice. The residual exploitation of amino acids by the olive orchard microbiome must also be considered as part of an environmentally friendly, integrated strategy to mitigate salinity stress. Full article

The incorporation of nucleoside analogs into DNA by polymerases, followed by their removal through base excision repair (BER), represents a promising strategy for cancer chemotherapy. In this study, we investigated the incorporation and cytotoxic effects of several nucleoside analogs—some of which are epigenetic reprogramming intermediates—in the U87 glioblastoma cell line. We found that two analogs, 5-hydroxymethyl-2′-deoxyuridine (5HmdU) and trifluorothymidine (TFT), are both cytotoxic and are efficiently incorporated into genomic DNA. In contrast, the 5-carboxy analogs—5-carboxy-2′-deoxyuridine (5CadU) and 5-carboxycytidine (5CadC)—showed no cytotoxicity and were not incorporated into DNA. Interestingly, 5-hydroxymethyl-2′-deoxycytidine (5HmdC) was cytotoxic but was not directly incorporated into DNA. Instead, it was deaminated into 5HmdU, which was then incorporated and likely responsible for the observed toxicity. 5HmdU is actively removed from DNA through the BER pathways. In contrast, TFT remains stably incorporated and is neither excised by BER nor does it hydrolyze into 5CadU—a known substrate for the DNA glycosylase SMUG1. We also found that N⁶-benzyladenosine (BzAdo), an inhibitor of the enzyme 2′-deoxynucleoside 5′-phosphate N-hydrolase (DNPH1), enhances the cytotoxicity of 5HmdU. However, the thymidine phosphorylase inhibitor tipiracil hydrochloride (TPI) does not increase the cytotoxic effect of TFT in U87 cells. Together, these findings highlight 5HmdU and TFT as promising chemotherapeutic agents for glioblastoma, each with distinct mechanisms of action and cellular processing. Full article

To enhance the anti-overturning performance of poles and prevent tilting or collapse, a prefabricated foundation for distribution lines is developed. Field tests are conducted on five groups of foundations. Based on the test results, finite element analysis (FEA) is employed to investigate the influence of different factors—such as pole embedment depth, foundation locations, soil type, and soil parameters—on the anti-overturning performance of pole prefabricated foundations. The results indicate that under ultimate load conditions, the reaction force distribution at the base of the foundation approximates a triangular pattern, and the lateral earth pressure on the pole follows an approximately quadratic parabolic distribution along the depth. When the foundation size increases from 0.8 m to 0.9 m, the bearing capacity of the prefabricated foundation improves by 8%. Furthermore, when the load direction changes from 0° to 45°, the foundation’s bearing capacity increases by 14%. When the foundation is buried at a depth of 1.0 m, compared with the ground position, the ultimate overturning moment of the prefabricated foundation increases by 10%. Based on field test results, finite element simulation results, and limit equilibrium theory, a calculation method for the anti-overturning bearing capacity of prefabricated pole foundations is developed, which can provide a practical reference for the engineering design of distribution line poles and their prefabricated foundations. Full article

Context: Many patients at the end of life receive antibiotics to alleviate symptoms and improve quality of life; however, clear guidelines supporting decision making about the use of antibiotics are still lacking. Objectives: This study aimed to evaluate the benefits and harms of antibiotic use among patients under a palliative care community support team in Portugal. Methods: An observational, cross-sectional, retrospective study was conducted on 249 patients who died over a two-year period, having been followed for at least 30 days prior to their death. Data included patient demographics, clinical diagnoses, antibiotic prescriptions, and symptomatic outcomes. The effects of commonly prescribed antibiotics—amoxicillin + clavulanic acid, cefixime, ciprofloxacin, and levofloxacin—were compared using statistical analyses to assess survival, symptom intensity, and functional scales. Results: Adverse events, primarily infections and secretions, occurred in 57.8% of cases, with 33.7% receiving antibiotics. No significant difference in survival was observed across the antibiotic groups (p = 0.990). Symptom intensity significantly reduced after 72 h of treatment (p < 0.05), with ciprofloxacin demonstrating the greatest symptom control. The Palliative Outcome Scale decreased uniformly, with higher scores associated with amoxicillin + clavulanic acid (p = 0.004). The Palliative Performance Scale declined post-treatment, with significant changes noted for cefixime and ciprofloxacin (p < 0.05). Conclusions: Antibiotics may improve symptom control and quality of life in the end-of-life stage. While second-line antibiotics may offer additional benefits, the heterogeneity of the sample and limited adverse effect data underscore the need for further research to guide appropriate prescription practices in palliative care. Full article

There is insufficient evidence regarding the cytotoxicity of restorative 3D-printing resins, used as part of the digital workflow in dentistry. This study presents a novel comparative evaluation of cell viability and adhesion using human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs), a less commonly used but clinically relevant cell line in dental biomaterials research. The aim of this study was to evaluate the cell viability of WJ-MSCs seeded on 3D-printed resins intended for temporary restorations. Resin discs of three commercial 3D-printing resins (NextDent C&B, Leaf Dental C&B, and UNIZ Temp) and a conventional self-curing acrylic resin (NicTone) were used. WJ-MSCs were cultured on the specimens for 1, 4, and 10 days. Cell viability was assessed using the PrestoBlue assay, Live/Dead immunofluorescence staining, and 7AAD/Annexin V staining. Cell adhesion was evaluated using scanning electron microscopy. Direct exposure to the 3D-printed resins and the self-curing acrylic caused slight reductions in cell viability compared to the control group in both microscopic analyses. 7AAD/Annexin V showed the highest percentage of viable WBCs for the conventional acrylic (34%), followed by UNIZ (35%), NextDent (42%), and Leaf Dental (36%) (ANOVA p < 0.05 Tukey’s post-hoc test p < 0.05). These findings suggest that 3D-printed resins could be considered safe for use in temporary restorations. Full article

Understanding the alterations to the shoot and root traits of rapeseed (Brassica napus) in response to salt stress is vital for improving its ability to thrive in saline-prone regions. This research aims to evaluate the responses of shoot and root traits of rapeseed at the vegetative stage under salt- and salicylic acid-induced stress in hydroponic culture. Five parents and ten F₃ segregants of rapeseed were subjected to three treatments: T1: control, T2: 8 dSm⁻¹ salt, and T3: 8 dSm⁻¹ salt + 0.1 mM salicylic acid at 21 days of age. Salinity stress significantly reduced the estimated root surface area by 54% compared to control, highlighting the plasticity of roots under stress. The simultaneous application of salt and SA did not alleviate the salinity stress, but rather reinforced the degree of stress and decreased the number of leaves, diameter of the main axis, chlorophyll content, and estimated root surface area by 18.5%, 15.4%, 38.8%, and 23%, respectively, compared to T2. The parental genotype M-245 followed by F₃ genotype M-232×M-223 accounted for the higher overall estimated root surface area. These results provide novel insights into the responses of root traits in rapeseed breeding lines under dual treatment, which hold promising implications for future rapeseed breeding efforts focused on sustainable rapeseed production. Full article

Phosphatidylinositol-3-kinase (PI3K) inhibition has emerged as a therapeutic option against indolent lymphoma, including relapsed follicular lymphoma (FL). While inhibition of active signaling in the lymphoma cell represents the primary mode of action, PI3K inhibition also exerts immunomodulatory effects. Here we have analyzed 17 consecutive advanced treatment line FL patients treated with the delta-selective PI3K inhibitor idelalisib in a retrospective single-center observational study, with a specific focus on response and immune effects. Eleven patients achieved complete remission (CR) or partial remission (PR) with median response duration of 22 (11–88) months following a median idelalisib exposure of 15 (4–88) months. Disease response persisted in three patients for a median of 37 (21–63) months following cessation of idelalisib without another therapy being initiated. Autoimmune side effects occurred in eight of the eleven patients who responded, compared to none in six patients whose disease did not respond. In conclusion, a time-limited exposure to idelalisib may induce sustained remissions in a portion of patients with recurrent and/or refractory (r/r) FL, suggesting immunomodulatory effects of PI3K inhibition to be involved in the control of the disease. Full article

Early printed books, particularly incunabula, are invaluable archives of the beginnings of modern educational systems. However, their complex layouts, antique typefaces, and page degradation caused by bleed-through and ink fading pose significant challenges for automatic transcription. In this work, we present a modular pipeline that addresses these problems by combining modern layout analysis and language modeling techniques. The pipeline begins with historical layout-aware text segmentation using Kraken, a neural network-based tool tailored for early typographic structures. Initial optical character recognition (OCR) is then performed with Kraken’s recognition engine, followed by post-correction using a fine-tuned ByT5 transformer model trained on manually aligned line-level data. By learning to map noisy OCR outputs to verified transcriptions, the model substantially improves recognition quality. The pipeline also integrates a preprocessing stage based on our previous work on bleed-through removal using robust statistical filters, including non-local means, Gaussian mixtures, biweight estimation, and Gaussian blur. This step enhances the legibility of degraded pages prior to OCR. The entire solution is open, modular, and scalable, supporting long-term preservation and improved accessibility of cultural heritage materials. Experimental results on 15th-century incunabula show a reduction in the Character Error Rate (CER) from around 38% to around 15% and an increase in the Bilingual Evaluation Understudy (BLEU) score from 22 to 44, confirming the effectiveness of our approach. This work demonstrates the potential of integrating transformer-based correction with layout-aware segmentation to enhance OCR accuracy in digital humanities applications. Full article

Background/Objectives: Anti-tumour necrosis factor (anti-TNF) medications were historically commonly prescribed as the first-line biologic treatment for chronic inflammatory pouch conditions. However, their use in these conditions is mainly based on retrospective studies of relatively small numbers of patients with short follow up periods. We aimed to describe the long-term outcomes of first-line anti-TNF therapy in a large, multi-centre, multi-national patient cohort with chronic inflammatory pouch conditions. Methods: This was an observational, retrospective, multi-centre, multi-national study. We included patients with chronic inflammatory pouch conditions initially treated with anti-TNF drugs infliximab (IFX) or adalimumab (ADA), who had a follow up of at least 1 year. The primary outcome was anti-TNF treatment persistence, defined as continuation of anti-TNF throughout the study period. The secondary outcome was pouch failure, defined by the need for a defunctioning ileostomy or pouch excision. Results: We recruited 98 patients with chronic inflammatory pouch conditions initially treated with anti-TNF medications—63 (64.3%) treated with IFX and 35 (35.7%) treated with ADA. Average follow up length was 94.2 months (±54.5). At the end of the study period only 22/98 (22.4%) patients were still on anti-TNF treatment. In those in whom the first-line anti-TNF was discontinued, the median time to discontinuation was 12.2 months (range 5.1–26.9 months). The most common cause for anti-TNF discontinuation was lack of efficacy despite adequate serum drug levels and absence of anti-drug antibody formation (30 patients, 30.6%). Loss of response due to anti-drug antibody formation was the cause for discontinuation in 18 patients (18.4%), while 12 patients (12.2%) stopped treatment because of adverse events or safety concerns. Out of the 76 patients discontinuing anti-TNF treatment, 34 (34.7% of the cohort) developed pouch failure, and 42 (42.8% of the cohort) are currently treated with a different medical therapy. Conclusions: First-line anti-TNF therapy for chronic pouch inflammatory conditions is associated with low long-term persistence rates. This is due to a combination of lack of efficacy and adverse events. A significant percentage of patients initially treated with anti-TNF therapy develop pouch failure. Full article

Nephrogenic diabetes insipidus (NDI) is a rare hereditary disorder characterized by renal resistance to arginine vasopressin (AVP), resulting in the kidneys’ inability to concentrate urine. Approximately 90% of NDI cases follow an X-linked inheritance pattern and are associated with pathogenic variants in the AVPR2 gene, which encodes the vasopressin receptor type 2. The remaining 10% are attributed to mutations in the AQP2 gene, which encodes aquaporin-2, and may follow either autosomal dominant or recessive inheritance patterns. We present the case of a male infant, younger than nine months of age, who was clinically diagnosed with NDI at six months. The patient presented recurrent episodes of polydipsia, polyuria, dehydration, hypernatremia, and persistently low urine osmolality. Despite adjustments in pharmacologic treatment and strict monitoring of urinary output, the clinical response remained suboptimal. Given the lack of improvement and the radiological finding of an absent posterior pituitary (neurohypophysis), the possibility of coexistent central diabetes insipidus (CDI) was raised, prompting a therapeutic trial with desmopressin. Nevertheless, in the absence of clinical improvement, desmopressin was discontinued. The patient’s management was continued with hydrochlorothiazide, ibuprofen, and a high-calorie diet restricted in sodium and protein, resulting in progressive clinical stabilization. Whole-exome sequencing identified a novel homozygous missense variant in the AQP2 gene (c.398T > A; p.Val133Glu), classified as likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) criteria: PM2 (absent from population databases), PP2 (missense variant in a gene with a low rate of benign missense variation), and PP3 (multiple lines of computational evidence supporting a deleterious effect)]. NDI is typically diagnosed during early infancy due to the early onset of symptoms and the potential for severe complications if left untreated. In this case, although initial clinical suspicion included concomitant CDI, the timely initiation of supportive management and the subsequent incorporation of molecular diagnostics facilitated a definitive diagnosis. The identification of a previously unreported homozygous variant in AQP2 contributed to diagnostic confirmation and therapeutic decision-making. The diagnosis and comprehensive management of NDI within the context of polyuria-polydipsia syndrome necessitates a multidisciplinary approach, integrating clinical evaluation with advanced molecular diagnostics. The novel AQP2 c.398T > A (p.Val133Glu) variant described herein was associated with early and severe clinical manifestations, underscoring the importance of genetic testing in atypical or treatment-refractory presentations of diabetes insipidus. Full article

With the increasing detection of artemisinin resistance to front-line antimalarials in Africa and notwithstanding the planned roll-out of RTS’S and R21 in Africa, the search for new vaccines with high efficacy remains an imperative. Towards this endeavour, we performed in silico screening to identify Plasmodium falciparum gametocyte stage genes that could be targets of protection or diagnosis. Through the analysis we identified a gene, Pf3D7_1105800, coding for a Plasmodium falciparum subtilisin-like domain-containing protein (PfSDP) and thus dubbed the gene Pfsdp. Genetic diversity assessment revealed the Pfsdp gene to be relatively conserved across continents with signs of directional selection. Using RT qPCR and Western blots, we observed that Pfsdp is expressed in all developmental stages of the parasite both at the transcript and protein level. Immunofluorescence assays found PfSDP protein co-localizing with PfMSP-1 and partially with Pfs48/45 at the asexual and sexual stages, respectively. Further, we demonstrated that anti-PfSDP peptide-specific antibodies inhibited erythrocyte invasion by 20–60% in a dose-dependent manner, suggesting that PfSDP protein might play a role in merozoite invasion. We also discovered that PfSDP protein is immunogenic in children from different endemic areas with antibody levels increasing from acute infection to day 7 post-treatment, followed by a gradual decay. The limited effect of antibodies on erythrocyte invasion could imply that it might be more involved in other processes in the development of the parasite. Full article

(1) Background: Epidemiological studies link ozone (O₃) exposure to diabetes risk, but mechanisms and early biomarkers remain unclear. (2) Methods: Female mice exposed to 0.5/1.0 ppm O₃ were assessed for glucose tolerance and HOMA (homeostasis model assessment) index. Genes related to impaired glucose tolerance and insulin resistance were screened through the Comparative Toxicogenomics Database (CTD), and verified using quantitative real-time PCR. In addition, liver histopathological observations and the determination of basic biochemical indicators were conducted, and targeted metabolomics analysis was performed on the liver to verify glycogen levels and gene expression. In vitro validation was conducted with HepG2 and Min6 cell lines. (3) Results: Fasting blood glucose and insulin resistance were elevated following O₃ exposure. Given that the liver plays a critical role in glucose metabolism, we further investigated hepatocyte apoptosis and alterations in glycogen metabolism, including reduced glycogen levels and genetic dysregulation. Metabolomics analysis revealed abnormalities in fructose metabolism and glycogen synthesis in the livers of the O₃-exposed group. In vitro studies demonstrated that oxidative stress enhances both liver cell apoptosis and insulin resistance in pancreatic islet β cells. (4) Conclusions: O₃ triggers prediabetes symptoms via hepatic metabolic dysfunction and hepatocyte apoptosis. The identified metabolites and genes offer potential as early biomarkers and therapeutic targets. Full article

Background: The identification of pathogenic variants in the Breast Cancer Genes 1 and 2 (BRCA1/2) is a critical predictive biomarker for poly (ADP-ribose) polymerase inhibitor (PARPi) therapy in epithelial ovarian cancer (EOC). The aim of this study is to define real-world rates and determinants of germline and somatic BRCA1/2 testing and subsequent PARPi utilisation in Australia using a national clinical quality registry. Methods: This multi-centre cohort study analysed data from 1503 women with non-mucinous EOC diagnosed between May 2017 and July 2022, captured by the Australian National Gynae-Oncology Registry (NGOR). We evaluated rates of germline and somatic testing and PARPi use, using multivariate logistic regression to identify associated clinical and demographic factors. Results: Overall germline and somatic testing rates were 68% and 32%, respectively. For the high-grade serous ovarian cancer (HGSOC) cohort, rates were higher, at 78% and 39%, respectively. Germline testing was significantly less likely for women aged >80 years (OR 0.49), those in regional areas (OR 0.61), and those receiving single-modality treatment. Somatic testing uptake increased significantly following public reimbursement for PARPi (p = 0.004). Among eligible women with a newly diagnosed BRCA pathogenic variant and advanced disease (n = 110), 52% commenced first-line maintenance PARPi. Conclusions: This national study offers valuable insights into Australian ovarian cancer care, highlighting opportunities to enhance testing equity for older women (aged >80) and regional patients. Furthermore, it identifies the translation of a positive test into PARPi therapy as a complex area that warrants further collaborative investigation to optimise patient outcomes. Full article

Construction and demolition byproducts include substantial amounts of wood panel waste (WPW) that pose environmental challenges. They also create opportunities for sustainable resource recovery. This study investigates the potential of WPW-derived biochar as an efficient adsorbent for phenol removal from aqueous solutions. Biochar was produced via pyrolysis at 450 °C and subsequent activation at 750, 850, and 950 °C. The biochar’s physicochemical properties, including surface area, pore volume, and elemental composition, were characterized using advanced methods, including BET analysis, elemental analysis, and adsorption isotherm analysis. Activated biochar demonstrated up to nine times higher adsorption capacity than raw biochar, with a maximum of 171.9 mg/g at 950 °C under optimal conditions: pH of 6 at 25 °C, initial phenol concentration of 200 mg/L, and biochar dosage of 1 g/L of solution for 48 h. Kinetic and isotherm studies revealed that phenol adsorption followed a pseudo-second-order model and fit the Langmuir isotherm, indicating chemisorption and monolayer adsorption mechanisms. Leaching tests confirmed the biochar’s environmental safety, with heavy metal concentrations well below regulatory limits. Based on these findings, WPW biochar offers a promising, eco-friendly solution for wastewater treatment in line with circular economy and green chemistry principles. Full article

Background/Objectives: Humulus lupulus (hops) are a perennial, dioecious plant widely cultivated for beer production, used for their distinguishing aroma and bitterness—traits that confer high added value status. Various hop-derived compounds have been reported to exhibit antioxidant, antimicrobial, antiproliferative and other bioactive effects. This systematic review and meta-analysis assesses the impact of hop compounds on the viability of diverse cancer cell lines. Methods: A comprehensive literature search was performed following PRISMA guidelines. Data were synthesized via multivariate meta-analysis and meta-regression, using IC₅₀ values as the effect size. Key variables included assay type (SRB, tetrazolium salt-based, crystal violet), exposure duration (24, 48, 72 h), specific hop compound and cancer cell line. Results: Of 622 articles identified, 61 met eligibility criteria, yielding 354 individual experiments. Meta-regression of xanthohumol (XN) IC₅₀ values across SRB, tetrazolium and crystal violet assays revealed no statistically significant differences at 24 h (p = 0.77), 48 h (p = 0.35) and 72 h (p = 0.70), supporting the interchangeability of the methods. Meta-analysis confirmed that hop constituents inhibit cancer cell proliferation; XN emerged as the most potent flavonoid (IC₅₀ = 16.89 μM at 72 h), while lupulone was the strongest compound overall (IC₅₀ = 5.00 μM at 72 h). Crude hop extracts demonstrated greater antiproliferative selectivity for cancer versus non-cancer cells (IC₅₀ = 35.23 vs. 43.80 μg/mL at 72 h). Conclusions: Hop compounds, and particularly bitter acids, demonstrate promising antiproliferative activity against cancer cells with comparatively low toxicity to healthy cells. Furthermore, our analysis confirms the comparability of SRB, tetrazolium-based and crystal violet assays, supporting the robust integration of antiproliferative data. Full article