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.

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.

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.

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.

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

Percolation properties of two types of inhomogeneous k-mers with different arrangements of conductive and nonconductive sites on a triangular lattice is studied by Monte Carlo simulations. The depositing objects are ‘Janus’ k-mers, with one conductive and one nonconductive side, and ‘patchy’ k-mers, with conductive ends and a nonconductive middle. We find that the percolation threshold strongly depends on the k-mer length, the number of nonconductive sites, and their spatial distribution. For both object types, the percolation threshold increases with the fraction of nonconductive sites. For fixed number of nonconductive sites, the threshold decreases monotonicaly with the object length. The presence of pre-existing conductive objects on the substrate can either hinder or enhance percolation, depending on their size and concentration.

Introduction Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed the management of type 2 diabetes and obesity by improving glycemic control, promoting weight loss, and reducing cardiovascular risk. This study aimed to evaluate national trends in GLP-1 RA utilization and expenditure in Croatia between 2010 and 2024. Methods We conducted a nationwide, retrospective analysis using the International Medical Statistics and IQVIA pharmaceutical databases. Utilization was measured in defined daily doses per 1000 inhabitants per day, and financial expenditure was expressed in euros. Trends were contextualized within evolving clinical evidence, guideline recommendations, and healthcare reimbursement policies. Results Total noninsulin antidiabetic drug consumption more than doubled between 2010 and 2024, with the use of GLP-1 RAs rising from negligible at the time of market entry to that worth 15.99 defined daily doses per 1000 inhabitants per day in 2024, representing 16.1% of total prescriptions. Expenditure on GLP-1 RAs reached 42.07 million euros in 2024, accounting for 42.7% of total noninsulin antidiabetic spending. Semaglutide emerged as the dominant agent according to both utilization and cost, followed by dulaglutide and liraglutide. Obesity-specific indications were underutilized, largely due to lack of reimbursement. Conclusions GLP-1 RA prescribing has increased substantially in Croatia over the past decade, reflecting their growing therapeutic importance. However, economic constraints, restrictive reimbursement, and sociocultural barriers continue to limit access, particularly in obesity care. Our findings highlight the need to align reimbursement frameworks and clinical practice with emerging evidence to maximize the cardiometabolic and public health benefits of GLP-1 RAs.

Circadian rhythms regulate key biological processes central to cancer biology, including cell cycle control, DNA repair, metabolism, immune function, and drug pharmacokinetics. Experimental models consistently demonstrate marked time-of-day differences in the efficacy and toxicity of chemotherapy, targeted agents, and immunotherapies. Clinical studies of chronomodulated chemotherapy—particularly with fluoropyrimidines, platinum compounds, and anthracyclines—show reproducible reductions in treatment-related toxicity, while effects on survival outcomes remain variable and often sex dependent. Emerging clinical evidence also suggests that timing of immune checkpoint inhibitor administration may influence progression-free and overall survival across several tumor types. However, translation into routine oncology practice has been limited by interindividual variability in circadian phase, tumor-specific disruption of clock function, lack of validated biomarkers, and logistical constraints of time-specific drug delivery. Advances in circadian phenotyping, wearable monitoring, and adaptive dosing technologies now offer feasible pathways toward individualized, biology-driven treatment timing. This narrative review critically evaluates mechanistic, preclinical, and clinical evidence for chronotherapy across oncological treatment modalities and examines challenges and opportunities for its integration into precision cancer care.

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.

Abstract In armed conflict and other situations of armed violence, people with disabilities, both children and adults, face serious and unique threats to their mental health and psychosocial well-being, including due to being targeted because of their disability, their inability to flee attacks, risk of abandonment, breakdown of services, and lack of access to health care and assistive devices. Unequal access to the sparse mental health services and education that may exist during conflicts exacerbates mental health impacts, and children with disabilities experience multiple and intersecting forms of mental health harms based on their disability and age. Since 2015, Human Rights Watch has documented the mental health harms of armed conflict and armed violence on people with disabilities in Afghanistan, Cameroon, the Central African Republic, Palestine, South Sudan, Sudan, Syria, Ukraine and Yemen. While international mental and psychosocial support services standards call for inclusion and accessible services for all, people with disabilities are often the last to get support – this is especially true in cases of people with intellectual, psychosocial or hearing disabilities due to physical, communication and attitudinal barriers. There is an urgent need for governments, humanitarian donors and humanitarian agencies to change how they provide mental health and psychosocial support services in order to ensure that they are accessible to all.