Search Results (1,344)

Cutaneous and oral mucosal adverse events (AEs) are among the most common non-hematologic toxicities observed during breast cancer treatment. These complications arise across various therapeutic modalities including chemotherapy, targeted therapy, hormonal therapy, radiotherapy, and immunotherapy. Although often underrecognized compared with systemic side effects, dermatologic and mucosal toxicities can severely impact the patients’ quality of life, leading to psychosocial distress, pain, and reduced treatment adherence. In severe cases, these toxicities may necessitate dose reductions, treatment delays, or discontinuation, thereby compromising oncologic outcomes. The growing use of precision medicine and novel targeted agents has broadened the spectrum of AEs, with some therapies linked to distinct dermatologic syndromes and mucosal complications such as mucositis, xerostomia, and lichenoid reactions. Early detection, accurate classification, and timely multidisciplinary management are essential for mitigating these effects. This review provides a comprehensive synthesis of current knowledge on cutaneous and oral mucosal toxicities associated with modern breast cancer therapies. Particular attention is given to clinical presentation, underlying pathophysiology, incidence, and evidence-based prevention and management strategies. We also explore emerging approaches, including nanoparticle-based delivery systems and personalized interventions, which may reduce toxicity without compromising therapeutic efficacy. By emphasizing the integration of dermatologic and mucosal care, this review aims to support clinicians in preserving treatment adherence and enhancing the overall therapeutic experience in breast cancer patients. The novelty of this review lies in its dual focus on cutaneous and oral complications across all major therapeutic classes, including recent biologic and immunotherapeutic agents, and its emphasis on multidisciplinary, patient-centered strategies. Full article

Background/Objectives: Cancer suffers from unresolved therapeutic challenges owing to the lack of targeted therapies and heightened recurrence risk. This study aimed to investigate the new series of hydroxamate by structurally modifying the pharmacophore of vorinostat. Methods: The present work involves the synthesis of 15 differently substituted 2H-1,2,3-triazole-based hydroxamide analogs by employing triazole ring as a cap with varied linker fragments. The compounds were evaluated for their anticancer effect, especially their anti-breast cancer response. Molecular docking and molecular dynamics simulations were conducted to examine binding interactions. Results: Results indicated that among all synthesized hybrids, the molecule VI(i) inhibits the growth of MCF-7 and A-549 cells (GI₅₀ < 10 μg/mL) in an antiproliferative assay. Compound VI(i) was also tested for cytotoxic activity by employing an MTT assay against A549, MCF-7, and MDA-MB-231 cell lines, and the findings indicate its potent anticancer response, especially against MCF-7 cells with IC₅₀ of 60 µg/mL. However, it experiences minimal toxicity towards the normal cell line (HEK-293). Mechanistic studies revealed a dual-pathway activation: first, apoptosis (17.18% of early and 10.22% of late apoptotic cells by annexin V/PI analysis); second, cell cycle arrest at the S and G2/M phases. It also promotes ROS generation in a concentration-dependent manner. The HDAC–inhibitory assay, extended in silico molecular docking, and MD simulation experiments further validated its significant binding affinity towards HDAC 1 and 6 isoforms. DFT and ADMET screening further support the biological proclivity of the title compounds. The notable biological contribution of VI(i) highlights it as a potential candidate, especially against breast cancer cells. Full article

Background: Bimekizumab, secukinumab, and ixekizumab are IL-17-targeting biologics approved for the treatment of moderate-to-severe plaque psoriasis. While secukinumab and ixekizumab selectively inhibit IL-17A, bimekizumab targets both IL-17A and IL-17F, potentially providing greater anti-inflammatory efficacy. This study aimed to compare the real-world effectiveness, safety, and tolerability of these agents in a Polish dermatology center between 2019 and 2024. Methods: We conducted a retrospective analysis of 98 patients meeting at least one of the following criteria: PASI ≥ 10, BSA ≥ 10, DLQI ≥ 10, or involvement of special areas with inadequate response or contraindications to ≥2 systemic therapies. Patients with prior exposure only to IL-17 inhibitors were excluded. PASI, BSA, and DLQI scores were recorded at baseline, week 4, and week 12. Due to differences in dosing schedules, outcomes were aligned using standardized timepoints and exponential modeling of continuous response trajectories. Mixed-effects ANOVA was used to assess the influence of baseline factors (age, BMI, PsA status) on treatment outcomes. Adverse events were documented at each monthly follow-up visit. Results: Bimekizumab showed the greatest effect size for PASI reduction (Hedges’ g = 3.662), followed by secukinumab (2.813) and ixekizumab (1.986). Exponential modeling revealed a steeper response trajectory with bimekizumab (intercept = 0.289), suggesting a more rapid PASI improvement. The efficacy of bimekizumab was particularly notable in patients who were previously treated with IL-23 inhibitors. All three agents demonstrated favorable safety profiles, with no serious adverse events or discontinuations. The most frequent adverse events were mild and included upper respiratory tract infections and oral candidiasis. Conclusions: This real-world analysis confirmed that IL-17 inhibitors effectively improved PASI, BSA, and DLQI scores in moderate-to-severe psoriasis. Bimekizumab demonstrated the most rapid early improvements and a higher modeled likelihood of complete clearance, without significant differences at week 12. All agents were well tolerated, underscoring the need for further individualized, large-scale studies. Full article

Heavy metals are a major toxicological concern due to their adverse effects on human health, particularly in children exposed to contaminated areas. This study evaluated biomarkers of exposure in 253 children aged 6 to 12 from Magangue, Achi, and Arjona (Bolivar, Colombia), analyzing their relationship with neurotoxicity and hematological markers. The mean Pb concentrations at the study sites were 1.98 µg/g (Magangue) > 1.51 µg/g (Achi) > 1.24 µg/g (Arjona). A similar pattern was observed for Cd concentrations for Magangue (0.39 µg/g) > Achi (0.36 µg/g) > Arjona (0.14 µg/g). In contrast, Se concentrations followed a different trend for Arjona (0.29 µg/g) > Magangue (0.21 µg/g) > Achi (0.16 µg/g). The proportion of Se/Pb molar ratios > 1 was higher in Arjona (3.8%) than in Magangue (0.9%) and Achi (2.0%). For Se/Cd ratios, values > 1 were also more frequent in Arjona (70.7%), exceeding 20% in the other two locations. Significant differences were found among locations in red and white blood cell parameters and platelet indices. Neurotransmitter-related biomarkers, including serotonin, monoamine oxidase A (MAO-A), and acetylcholinesterase levels, also varied by location. Principal component analysis showed that Pb and Cd had high loadings on the same component as PLT, WBC, and RDW, and while Se loaded together with HGB, PDW, MCHC, MCH, and MCV, suggesting distinct hematological patterns associated with each element. Multiple linear regression analysis demonstrated a statistically significant inverse association between hair Pb levels and serotonin concentrations. Although MAO-A and Cd showed negative β coefficients, these associations were not statistically significant after adjustment. These findings highlight the potential impact of toxic element exposure on key hematological and neurochemical parameters in children, suggesting early biological alterations that may compromise health and neurodevelopment. Full article

Among the numerous compounds released as a result of human activities, endocrine-disrupting chemicals (EDCs) have attracted particular attention due to their widespread detection in human biological samples and their accumulation across various ecosystems. While early research primarily focused on their effects on reproductive health, it is now evident that EDCs may impact neurodevelopment, altering the integrity of neural circuits essential for cognitive abilities, emotional regulation, and social behaviors. These compounds may elicit epigenetic modifications, such as DNA methylation and histone acetylation, that result in altered expression patterns, potentially affecting multiple generations and contribute to long-term behavioral phenotypes. The effects of EDCs may occur though both direct and indirect mechanisms, ultimately converging on neurodevelopmental vulnerability. In particular, the gut–brain axis has emerged as a critical interface targeted by EDCs. This bidirectional communication network integrates the nervous, immune, and endocrine systems. By altering the microbiota composition, modulating immune responses, and triggering epigenetic mechanisms, EDCs can act on multiple and interconnected pathways. In this context, elucidating the impact of EDCs on neurodevelopmental processes is crucial for advancing our understanding of their contribution to neurological and behavioral health risks. Full article

Tillage is a major factor influencing soil biological communities, particularly earthworms, which play a key role in soil structure and nutrient cycling. To address soil degradation, less-intensive tillage practices are increasingly being adopted globally and have shown positive effects on earthworm populations when applied consistently over extended periods. However, understanding of the earthworm population dynamics in the period following the implementation of changes in tillage practices remains limited. This three-year field study (2021–2023) investigates earthworm populations during the early transition phase (4–6 years) following the conversion from conventional ploughing to conservation (<8 cm depth, with residue retention) and no-tillage systems in a temperate arable system in central Slovenia. Earthworms were sampled annually in early October from three adjacent fields, each following the same three-year crop rotation (maize—winter cereal + cover crop—soybeans), using a combination of hand-sorting and allyl isothiocyanate (AITC) extraction. Results showed that reduced tillage practices significantly increased both earthworm biomass and abundance compared to conventional ploughing. However, a significant interaction between tillage and year was observed, with a sharp decline in earthworm abundance and mass in 2022, likely driven by a combination of 2022 summer tillage prior to cover crop sowing and extreme drought conditions. Juvenile earthworms were especially affected, with their proportion decreasing from 62% to 34% in ploughed plots and from 63% to 26% in conservation tillage plots. Despite interannual fluctuations, no-till showed the lowest variability in earthworm population. Long-term monitoring is essential to disentangle management and environmental effects and to inform resilient soil management strategies. Full article

Developing innovative, low-cost halochromic materials for diagnosing microbial contamination in wounds and burns can effectively facilitate tissue regeneration. Here, we combine the pH-sensing capability of highly colorful red cabbage anthocyanins (RCAs) with their healing potential within a unique cellulose polymer film that mimics the skin matrix. Biological activities of RCA extract in bacterial cellulose (BC) showed no cytotoxicity and skin-sensitizing potential to human cells at concentrations of RCAs similar to those released from BC/RCA dressings (4.0–40.0 µg/mL). A decrease in cell viability and apoptosis was observed in human cancer cells with RCAs. The invisible eye detection of the early color change signal from RCAs in response to pH alteration by bacteria was recorded with a smartphone application. The incorporation of RCAs into BC polymer has altered the morphology of its matrix, resulting in a denser cellulose microfibril network. The complete coincidence of the vibrational modes detected in the absorption spectra of the cellulose/RCA composite with the modes in RCAs most likely indicates that RCAs retain their structure in the BC matrix. Affordable, sensitive halochromic BC/RCA hydrogels can be recommended for online monitoring of microbial contamination, making them accessible to patients. Full article

Spodoptera eridania (Stoll, 1781) (Lepidoptera: Noctuidae) is an important pest with a broad host range and growing relevance due to its high dispersal capacity, recent invasions into Africa and Asia, and documented resistance to biological insecticides. Here, we assessed S. eridania flight phenology and seasonal dynamics in the Florida Panhandle, using pheromone trapping data to evaluate population trends and environmental drivers. Moths were collected year-round, showing consistent patterns across six consecutive years, including two distinct annual flight peaks: an early crop season flight around March, and a more prominent flight peak during September–October. Moth abundance followed a negative quadratic relationship with temperature, with peak activity occurring between 15 °C and 26 °C. No significant relationship was found with precipitation or wind. These results underscore the strong influence of abiotic factors, particularly temperature, on seasonal abundance patterns of this species. Our findings offer key insights by identifying predictable periods of high pest pressure and the environmental conditions that drive population increases. Understanding the flight phenology and behavior of this species provides an ultimate contribution to the development of effective IPM and insect resistance management (IRM) programs, promoting the development of forecasting tools for more effective, timely pest management interventions. Full article

Chilling injury (CI) frequently occurs in postharvest flat peach fruit during cold storage, leading to quality deterioration and a reduced shelf life. Therefore, investigating the key factors involved in alleviating CI and developing effective preservatives are vital scientific issues for the industry. 2,4-Epibrassinolide (EBR) is a crucial endogenous hormone involved in plant response to both biological and environmental stressors. At present, most studies focus on the mechanisms of mitigating CI using a single concentration of EBR treatment, while few studies focus on the effects varying EBR concentrations have on CI. The purpose of this research is to explore the effects of varying concentrations of EBR on the postharvest quality and cold resistance of peach fruit, thereby establishing a basis for refining a technical framework of environmentally sustainable strategies to mitigate postharvest CI. The results show that EBR treatment effectively inhibits the generation of reactive oxygen species (ROS) and malondialdehyde (MDA) by maintaining the activities of antioxidant enzymes such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), thereby delaying the internal browning process of postharvest peaches. In addition, EBR treatment reduced the consumption of total phenolics by inhibiting the activities of polyphenol oxidase (PPO) and phenylalanine ammonia lyase (PAL). Experimental results identify that 5 μmol L⁻¹ EBR treatment emerged as the most effective concentration for maintaining core postharvest quality attributes. It significantly delayed the decrease in firmness, reduced weight loss, effectively inhibited the production of H₂O₂ and O₂⁻·, particularly during the early storage period, strongly restrained the activity of PAL, and maintained lower rot rates and internal browning indexes. While the 15 μmol L⁻¹ EBR treatment enhanced antioxidant activity, increased total phenolic content at certain stages, and maintained higher soluble solids and acid content, its effects on key physical quality parameters, like firmness and weight loss, were less pronounced compared to the 5 μmol L⁻¹ treatment. Full article

About one billion people worldwide are affected by neurologic disorders. Among the various neurologic disorders, one of the most common is Alzheimer’s disease (AD). AD is a neurodegenerative disorder that progressively affects cognitive functions, disrupting the daily lives of millions of individuals. Mild cognitive impairment (MCI) is often considered a prodromal stage of Alzheimer’s disease. In this article, we retrieved data from the online available dataset GSE63060, which includes transcriptomic data of 329 blood samples, of which there are 104 cognitively normal controls, 80 MCI patients, and 145 AD patients. We used transcriptomic data related to all three groups to perform an over-representation analysis of the gene ontologies followed by a network analysis. The aim of our study is to pinpoint alterations, detectable through a non-invasive method, in biological processes affected in MCI that persist during AD. Our goal is to uncover transcriptomic changes that could support earlier diagnosis and the development of more effective therapeutic strategies, starting from the early stages of the disease, to slow down or mitigate its progression. Our work provides a consistent picture of the transcriptomic unbalance of many genes strongly involved in ribosomal formation and biogenesis and splicing processes both in patients with MCI and with AD. Full article

Background/Objectives: This study aims to present a structured clinical workflow for offline adaptive Biology-guided Radiotherapy (BgRT) using the RefleXion X1 PET-linac system, addressing challenges introduced by inter-treatment anatomical and biological changes. Methods: We propose a decision tree offline adaptation framework based on real-time assessments of Activity Concentration (AC), Normalized Target Signal (NTS), and bounded dose-volume histogram (bDVH%) metrics. Three offline strategies were developed: (1) preemptive adaptation for minor changes, (2) partial re-simulation for moderate changes, and (3) full re-simulation for major anatomical or metabolic alterations. Two clinical cases demonstrating strategies 1 and 2 are presented. Results: The preemptive adaptation strategy was applied in a case with early tumor shrinkage, maintaining delivery parameters within acceptable limits while updating contours and dose distribution. In the partial re-Simulation case, significant changes in PET signal necessitated a same-day PET functional modeling session and plan re-optimization, effectively restoring safe deliverability. Both cases showed reduced target volumes and improved OAR sparing without additional patient visits or tracer injections. Conclusions: Offline adaptive workflows for BgRT provide practical solutions to address inter-fractional changes in tumor structure and function. These strategies can help maintain the safety and accuracy of BgRT delivery and support clinical adoption of PET-guided radiotherapy, paving the way for future online adaptive capabilities. Full article

Transcranial direct current stimulation (tDCS) can modulate cortical excitability in a polarity-specific manner, yet identical protocols often produce inconsistent outcomes across sessions or individuals. This narrative review proposes that much of this variability arises from the brain’s intrinsic temporal landscape. Integrating evidence from chronobiology, sleep research, and non-invasive brain stimulation, we argue that tDCS produces reliable, polarity-specific after-effects only within a circadian–homeostatic “window of efficacy”. On the circadian (Process C) axis, intrinsic alertness, membrane depolarisation, and glutamatergic gain rise in the late biological morning and early evening, whereas pre-dawn phases are marked by reduced excitability and heightened inhibition. On the homeostatic (Process S) axis, consolidated sleep renormalises synaptic weights, widening the capacity for further potentiation, whereas prolonged wakefulness saturates plasticity and can even reverse the usual anodal/cathodal polarity rules. Human stimulation studies mirror this two-process fingerprint: sleep deprivation abolishes anodal long-term-potentiation-like effects and converts cathodal inhibition into facilitation, while stimulating at each participant’s chronotype-aligned (phase-aligned) peak time amplifies and prolongs after-effects even under equal sleep pressure. From these observations we derive practical recommendations: (i) schedule excitatory tDCS after restorative sleep and near the individual wake-maintenance zone; (ii) avoid sessions at high sleep pressure or circadian troughs; (iii) log melatonin phase, chronotype, recent sleep and, where feasible, core temperature; and (iv) consider mild pre-heating or time-restricted feeding as physiological primers. By viewing Borbély’s two-process model and allied metabolic clocks as adjustable knobs for plasticity engineering, this review provides a conceptual scaffold for personalised, time-sensitive tDCS protocols that could improve reproducibility in research and therapeutic gain in the clinic. Full article

Background/Objectives: Maternal exposures are known to influence the risk of isolated cleft lip with or without cleft palate (CL/P)—a common and highly heritable birth defect with a multifactorial etiology. Methods: To identify new risk loci, we conducted a genome-wide gene–environment interaction (GEI) analysis of CL/P with maternal smoking and vitamin use in Filipinos (N_cases = 540, N_controls = 260). Since GEI analyses are typically low in power and the results can be difficult to interpret, we applied multiple testing frameworks to evaluate potential GEI effects: a one degree-of-freedom (1df) GxE test, the 3df joint test, and the two-step EDGE approach. Results: While no genome-wide significant interactions were detected, we identified 11 suggestive GEIs with smoking and 24 with vitamin use. Several implicated loci contain biologically plausible genes. Notable interactions with smoking include loci near FEZF1, TWIST2, and NET1. While FEZF1 is involved in early neuronal development, TWIST2 and NET1 regulate epithelial–mesenchymal transition, which is required for proper lip and palate fusion. Interactions with vitamins encompass CECR2—a chromatin remodeling protein required for neural tube closure—and FURIN, a critical protease during early embryogenesis that activates various growth factors and extracellular matrix proteins. The activity of both proteins is influenced by folic acid. Conclusions: Our findings highlight the critical role of maternal exposures in identifying genes associated with structural birth defects such as CL/P and provide new paths to explore for CL/P genetics. Full article

Background/Objectives: This study investigates the utility of multiparametric PET/MRI in delineating changes in physiologically distinct intratumoral habitats during trastuzumab-induced alterations in a preclinical HER2+ breast cancer model. Methods: By integrating diffusion-weighted MRI, dynamic contrast-enhanced MRI, [¹⁸F]Fluorodeoxyglucose- and [¹⁸F]Fluorothymidine-PET, voxel-wise parametric maps were generated capturing cellular density, vascularity, metabolism, and proliferation. BT-474 tumor-bearing mice have high expression of HER2 and, in response to trastuzumab, an anti-HER2 antibody, effectively show changes in proliferation and tumor microenvironment alterations that result in decreases in tumor volume through time. Results: Single imaging metrics and changes in metrics were incapable of identifying treatment-induced alterations early in the course of therapy (day 4) prior to changes in tumor volume. Hierarchical clustering identified five distinct tumor habitats, which enabled longitudinal assessment of early treatment response. Tumor habitats were defined based on imaging metrics related to biology and categorized as highly vascular (HV), hypoxic responding (HRSP), transitional zone (TZ), active tumor (ATMR) and responding (RSP). The HRSP cluster volume significantly decreased in trastuzumab-treated tumors compared to controls by day 4 (p = 0.015). The volume of ATMR cluster was significantly different at baseline between cohorts (p = 0.03). The TZ cluster, indicative of regions transitioning more to necrosis, significantly decreased in treated tumors (p = 0.031), suggesting regions had already transitioned. Multiparametric image clustering showed a significant positive linear correlation with histological multiparametric mapping, with R² values of 0.56 (HRSP, p = 0.013, 0.64 (ATMR, p = 0.0055), and 0.49 (responding cluster, p = 0.024), confirming the biological relevance of imaging-derived clusters. Conclusions: These findings highlight the potential utility of multiparametric PET/MRI to capture biological alterations prior to any single imaging metric which has potential for better understanding longitudinal changes in biology, stratifying tumors based on those changes, optimizing therapeutic monitoring and advancing precision oncology. Full article

Sorghum halepense (L.) Pers. (common name Johnson grass) is a perennial invasive weed that causes great harm worldwide, and its allelopathy has been demonstrated in a series of experiments. The present study offers new insights into its organ-specific phytochemical profiles using state-of-the-art metabolomic technology and explores the effects of a methanol extract of S. halepense rhizomes (ShER) and its major bioactive compounds (p-hydroxybenzoic acid and chlorogenic acid) on three noxious weed species. The phytotoxic effects of ShER are reflected through the inhibition of seed germination and reduced seedling growth, which are accompanied by changes in the antioxidant system of seedlings. Phytotoxicity is species specific and concentration dependent, and it is more pronounced against Chenopodiastrum murale (L.) S. Fuentes, Uotila & Borsch and Datura stramonium L. than highly tolerant Amaranthus retroflexus L. Catalase (CAT) is most likely the major mediator in the removal of reactive oxygen species, which are generated during germination and early seedling growth of Ch. murale exposed to ShER. The results of the present study imply the high potential of ShER in the management of amaranthaceous and solanaceous weeds, such as Ch. murale and D. stramonium, respectively. The present study offers an environmentally friendly solution for the biological control of weeds belonging to the families Amaranthaceae and Solanaceae. Also, the results of this research highlight the possibility of effective management of S. halepense by using it as a feedstock for bioherbicide production. Full article