Infrasound, defined as acoustic waves below 20 Hz, has been documented to influence human physiology and perception, yet remains largely absent from architectural discourse. This review synthesizes cross-disciplinary evidence from acoustics, physiology, and environmental psychology to reposition infrasound as a legitimate architectural design concern.. Findings show that everyday building services—compressors, HVAC systems, and ventilation fans—generate persistent low‑frequency fields that interact with room geometry, producing localized resonance “hot spots.” These amplified zones overlap with resonance ranges of the human body and neural rhythms, contributing to discomfort, fatigue, or subtle cognitive modulation. Evidence remains heterogeneous, and individual sensitivity varies, yet the architectural significance lies in recognizing buildings as resonant systems that can unintentionally sustain infrasonic fields. The study advocates integrating low‑frequency awareness into design workflows, service placement, room proportioning, and post‑occupancy evaluations, reframing infrasound as a spatial and environmental variable within salutogenic and evidence‑based architecture.

Chimeric antigen receptor (CAR) therapies have shown great success in hematological malignancies but remain largely ineffective against solid tumors such as pancreatic ductal adenocarcinoma (PDAC). A key obstacle among various aspects, is the dense stromal barrier formed by cancer-associated fibroblasts (CAFs), providing a rationale for simultaneously targeting stroma and tumor cells. Using immunohistochemistry of primary PDAC tumors and liver metastases, we confirmed high mesothelin (MSLN) expression on tumor cells, and CD70 expression on tumor cells and predominantly CAFs. Based on these results and the favorable safety profile of CAR natural killer (NK) cells over CAR T cells, we generated MSLN- and CD70-targeting IL-15-armored CAR NK cells. Both constructs mediated cytotoxicity against different pancreatic cancer and CAF cell lines with varying antigen expression in vitro, demonstrating that both, the CAR-molecule and IL-15 were required to increase functionality against more treatment-resistant cell lines. Interestingly, pooled MSLN- and CD70-CAR NK cells did not significantly improve cytolysis compared to monotherapies in an advanced 3D in vitro model or in vivo. Together these findings highlight the limitations of dual-targeting approaches and underscore the need for advanced engineering strategies to improve CAR NK cells beyond antigen targeting and cytokine support in the PDAC microenvironment.

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants that can disrupt human hepatic metabolism both directly and through alterations of the gut microbiota. However, the contribution of microbiota-mediated mechanisms to PFAS-induced hepatic dysfunction remains poorly understood. Here, we investigated how PFAS-modified gut microbial metabolites affect human hepatocyte metabolism using an in vitro colon fermentation model, supported by an in vivo mouse and in vitro human hepatocyte exposure studies. PFAS exposure altered the fecal metabolome in human colonic fermentations, particularly affecting pathways related to fatty acid, amino acid, vitamin, and mitochondrial metabolism. Fecal metabolomics from PFOA-exposed mice showed overlapping pathway-level alterations, including effects on fatty acid, bile acid, and steroid hormone metabolism, supporting the biological relevance of the in vitro findings. Exposure of HepaRG hepatocytes to control fermentation extracts markedly altered lipid profiles, confirming that gut-derived metabolites actively regulate hepatic metabolism. Notably, PFAS-exposed fermentation extracts induced distinct hepatocyte metabolic changes compared with PFAS-spiked control extracts, indicating effects driven by PFAS-modified microbial metabolites rather than direct PFAS carry-over. These changes included decreased acyl-carnitines and increased L-carnitine, consistent with altered fatty acid transport and mitochondrial β-oxidation. PFAS-modified extracts also altered bile acids, steroid metabolites, inosine, and sialic acid derivatives, suggesting broader alteration of bile acid signaling, endocrine-related metabolism, purine metabolism, glycoprotein turnover, and lipid-glucose homeostasis. These findings from our pilot study demonstrate that PFAS exposure reshapes gut microbial metabolite profiles with downstream consequences for hepatocyte metabolism. Our findings provide new mechanistic insight into how PFAS may contribute to metabolic disorders.

INTRODUCTION The increasing recognition of peripheral GABAergic signaling has renewed interest in the vascular effects of benzodiazepines (BDZs), particularly in light of their frequent use during pregnancy. Although BDZs have been studied in various vascular beds, their exact vasorelaxant mechanisms are still unclear. This study aimed to investigate the mechanisms underlying diazepam-induced vasodilation in human umbilical arteries (HUAs). METHODS Isolated endothelium-intact HUA rings were pre-contracted with serotonin, and concentration-response curves for diazepam (0.01-100 μM) were obtained using the tissue bath method. The roles of the endothelium, potassium and calcium channels, and TSPO were assessed using specific inhibitors or blockers: L-NAME, indomethacin, sildenafil, ODQ, glibenclamide, 4-aminopyridine, tetraethylammonium, and PK11195. The effects of diazepam pre-treatment on BaCl2-and serotonin-induced contractions were also investigated. RESULTS Diazepam induced a time- and concentration-dependent relaxation of HUA, with ⁓ 96% of the maximal effect being achieved at 100 μM. This response was endothelium-independent, as it was unaffected by eNOS or COX inhibition, but included an ODQ-sensitive component compatible with involvement of the soluble guanylate cyclase (sGC)-cGMP pathway. Potassium channel involvement was confirmed, and diazepam significantly suppressed BaCl2-and serotonin-induced contractions, suggesting calcium channel antagonism. PK11195 significantly attenuated diazepam-induced relaxation, implying involvement of TSPO. CONCLUSION Diazepam elicits near-complete relaxation in serotonin-precontracted HUA through endothelium-independent mechanisms that likely involve potassium channel activation, calcium channel inhibition, a component sensitive to ODQ suggesting possible involvement of the sGC-cGMP pathway, and interaction with TSPO. These results emphasize the remarkable vasoactivity of diazepam and its importance in the regulation of umbilical vascular tone.

Edible Natural Deep Eutectic Solvents (NADES) offer a route to ready-to-use extracts without solvent removal. This study examined how rational formulation design influences physicochemical properties, extraction performance, energy efficiency, thermal behavior, and cytocompatibility during bioactive recovery from Nigella sativa seeds. Twelve formulations spanning malic acid–polyol, citric acid–polyol, binary polyol, and ternary acid–polyol families were evaluated under standardized ultrasound-assisted conditions and compared with ethanolic ultrasound-assisted extraction, Soxhlet extraction, and cold-pressed oils. Selected NADES formulations outperformed the conventional systems. E1 (malic acid:glycerol:water) achieved the highest total phenolic content and lowest specific energy consumption (40.00 kJ mg−1 GAE), below the Soxhlet benchmark (55.17 kJ mg−1 GAE), whereas E9 (glycerol:xylitol:water) exhibited the greatest ABTS activity. Neat-NADES apparent pH and viscosity were inversely associated with total phenolic content, while viscosity and density were inversely associated with ABTS activity. ATR-FTIR showed stable, solvent-dominated fingerprints over 15 days, whereas DSC better differentiated neat NADES from their extracts. Most systems remained cytocompatible at 10,000× dilution, while acid–polyol formulations reduced viability at 500×; partial neutralization of N5/E5 restored viability. NADES performance was formulation- and application-dependent, requiring joint optimization of composition, acidity, viscosity, energy efficiency, and biologically compatible concentration.

Colorectal cancer remains a leading cause of cancer-related mortality worldwide, with automated polyp classification from endoscopic images offering a promising avenue for improving early detection. Existing approaches rely on single convolutional neural network (CNN) backbones with manually designed classification heads, limiting both representational capacity and deployment flexibility. This paper presents a swarm intelligence-augmented multi-backbone deep learning framework for eight-class gastrointestinal lesion classification on the Kvasir benchmark. Four CNN backbones (ResNet50, DenseNet121, MobileNetV2, EfficientNetB3) are independently fine-tuned using a two-phase transfer learning protocol and their penultimate-layer features concatenated into a 5888-dimensional representation, reduced to 256 dimensions via PCA. Five swarm intelligence algorithms—Particle Swarm Optimization, Artificial Bee Colony, JADE, L-SHADE, and CMA-ES—are benchmarked on the classification head architecture search task; all independently converge to tanh activation, a consistent pattern across independently initialized algorithms that is suggestive of, though not conclusive evidence for, particular geometric properties of PCA-transformed deep feature spaces. The PSO-optimized single-layer head (284 units, tanh) outperforms a manually designed three-layer baseline by 0.75% while using 67% fewer parameters. SI-guided class weight optimization yields targeted F1 improvements on the two most clinically significant classes (polyps: +0.015, ulcerative-colitis: +0.013). The fixed-head classifier trained on fused four-backbone features achieves 91.08% accuracy on Kvasir v2 (multi-seed mean 91.47% ± 0.49 across nine converging seeds; one seed failed to converge and is disclosed rather than excluded), below end-to-end DenseNet121 (92.25%; Wilcoxon p = 0.31, not statistically significant), while enabling classifier updates in under 30 s; a three-backbone subset dropping the weakest backbone (EfficientNetB3) reaches 92.33%, exceeding the full four-backbone fusion. Cross-dataset evaluation on Kvasir v1-to-v2 confirms near-zero generalization gaps across dataset scales; a restricted two-class evaluation on HyperKvasir (the only two of eight classes with usable labeled data) reaches 96.28% accuracy, and dual Grad-CAM with SI minimal sufficient region analysis, validated quantitatively against Kvasir-SEG ground-truth masks, provides spatially grounded, clinically interpretable explanations.

The rapid growth of e-commerce has intensified last-mile delivery activities in urban areas, creating challenges for city logistics systems related to operational efficiency, congestion, and environmental impacts. In this context, understanding the factors that influence customer satisfaction with logistics operators is increasingly important, as mismatches between customer expectations and delivery service characteristics may lead to operational inefficiencies such as failed delivery attempts and repeated delivery rounds. This study proposes a machine learning framework for predicting customer satisfaction with postal and logistics operators in urban delivery systems using survey data on customer characteristics, preferences, and service perceptions. Several machine learning algorithms were developed and evaluated to identify the key determinants of customer satisfaction and assess their predictive performance. Beyond predictive accuracy, the study interprets customer satisfaction as an indicator of the alignment between customer expectations and delivery service configurations. Improved alignment may support service configurations that reduce delivery mismatches and repeated delivery attempts, which are recognized as a significant source of additional transport activity in urban freight systems. By identifying customer segments whose expectations are not adequately addressed by existing delivery services, the proposed framework can support more informed service design and operational decision-making. From a city logistics perspective, the potential reduction in failed deliveries and repeated delivery rounds may contribute to lower vehicle kilometers travelled, congestion, energy consumption, and emissions associated with urban freight transport, although these operational and environmental indicators were not directly measured in this study. The proposed approach therefore provides a data-driven decision-support tool that can help operators improve service quality and serve as a basis for future integration with operational and environmental indicators in sustainable last-mile delivery planning.

Simple Summary The biodiversity of bats in Bosnia and Herzegovina has only been assessed by methods that require capture and/or the analysis of echolocation signals, thus giving and incomplete picture of the true biodiversity. To address this, we aimed to measure bat diversity by analyzing DNA from bat droppings (guano) and comparing the results of this advanced genetic method to traditional morphological measurements of captured bats. The results revealed that while the morphological method identified only 10 bat species, the DNA analysis successfully identified 13 species—including Mehely’s horseshoe bat, a species never recorded in the country before. Furthermore, DNA testing clarified uncertain morphological identifications and discovered more species at every location. The study concludes that Bosnia and Herzegovina hosts a much richer diversity of bats than previously thought, and proves that non-invasive DNA sampling from guano is a highly effective tool for routine bat monitoring and provides an easy, harmless way for conservationists to pinpoint and protect critical natural habitats, ensuring the survival of these ecologically vital animals and maintaining healthy local ecosystems.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of diffuse large B ‐ cell lymphoma (DLBCL) characterized by infiltration of malignant B cells into the central nervous system (CNS). 1 Fit patients are treated with high ‐ dose methotrexate (HD ‐ MTX) – based polychemotherapy followed by thiotepa ‐ containing high ‐ dose chemotherapy and autologous stem cell transplantation (ASCT). 2 For patients unsuitable for ASCT, induction treatment is consolidated with high ‐ dose cytarabine and low ‐ dose whole ‐ brain radiotherapy (WBRT). 1,2 Patients unsuitable for HD ‐ MTX can receive first ‐ line treatment with a single alkylator, such as temozolomide (TMZ) and WBRT. Despite therapeutic advances and high response rates, over half of the patients with PCNSL relapse within 2 years after diagnosis. 3 TMZ maintenance treatment has been suggested to reduce relapse rates and improve overall survival (OS) for patients with post ‐ induction complete remission (CR) or partial remission (PR). Therefore, its administration is supported by international guidelines, including the European Hematology Association and European Society for Medical Oncology (EHA ‐ ESMO) joint recommendations 2 and the National Comprehensive Cancer Network (NCCN) Guidelines for B ‐ Cell Lymphomas (Version 3.2026). However, implementation of TMZ maintenance varies across clinical settings, allowing real ‐ world evaluation of the association between TMZ

GLP-1 receptor agonist–based therapy is of interest in Polyendocrine Metabolic Ovarian Syndrome (PMOS; formerly polycystic ovary syndrome [PCOS]) because obesity and insulin resistance may worsen hyperandrogenism, anovulation, and infertility. To systematically review randomized controlled trial evidence on the effects of GLP-1 receptor agonists on ovulatory function and reproductive hormonal parameters in women with Polyendocrine Metabolic Ovarian Syndrome. PubMed was searched from database inception to February 3, 2026. Eligible English-language randomized controlled trials included women with Polyendocrine Metabolic Ovarian Syndrome diagnosed according to established PCOS diagnostic criteria used in the original randomized controlled trials and compared a GLP-1 receptor agonist, alone or in combination with metformin, with metformin or placebo, reporting reproductive hormonal, menstrual, ovulatory, or pregnancy-related outcomes. Five randomized controlled trials involving 418 participants were included. Interventions used liraglutide or exenatide over 12–32 weeks. GLP-1 receptor agonist–based therapy was associated with improvements in body weight, body mass index, waist circumference, glucose parameters, insulin resistance, increased sex hormone-binding globulin, and reduced free androgen index. Menstrual cycle frequency, regularity, and recovery improved across studies; however, ovulation was not directly or consistently assessed. Pregnancy outcomes were reported in only two heterogeneous trials and appeared favorable versus metformin alone. GLP-1 receptor agonists appear promising for improving metabolic, androgen-related, and menstrual parameters in women with Polyendocrine Metabolic Ovarian Syndrome, but current evidence remains limited for direct ovulatory and fertility outcomes.

The important cereal pathogen Fusarium graminearum is not only able to produce trichothecene toxins, like deoxynivalenol, but also the plant hormone auxin (indole‐3‐acetic acid, IAA). Highly elevated levels of IAA and auxin derivatives such as IAA‐glucoside or IAA amino‐acid conjugates were observed in the susceptible wheat cultivar Apogee infected with F. graminearum. We report here that the fungal pathogen can hydrolyse tryptamine‐derived hydroxycinnamic acid amides produced in high amounts during plant defence and is able to convert the released tryptamine in high yield into IAA. We investigated the role of copper amine‐oxidase candidate genes, which code for enzymes converting tryptamine into the IAA precursor indole‐3‐acetaldehyde. After consecutive knock‐out of seven copper amine oxidases the resulting septuple‐mutant strain (aoxΔ7) had strongly reduced ability to produce auxin from tryptamine in vitro. Virulence of the aoxΔ7 mutant was significantly impaired while deoxynivalenol production in planta was comparable to the wild type. Our results indicate that F. graminearum, formerly presumed to be a toxin‐producing necrotroph, in an early biotrophic phase uses subterfuge by converting abundantly formed plant defence compounds into defence‐suppressing auxin.