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Cellulose nanofiber/polyacrylic acid (CNF/PAA) hydrogel-based colorimetric sensor was fabricated for non-invasive screening of prostate cancer (PCa) via selective detection of sarcosine. The hydrogel was synthesized by photo-crosslinking of acrylic acid in the presence of CNF which acted as mechanical reinforcement and as color enhancer. The hydrogel exhibited a high aqueous absorption and high mechanical strength. A homogeneous distribution of CNF in the hydrogel was confirmed by TEM. A significant improvement in the compressive modulus and stress in the hydrogel were obtained after the incorporation of 0.25%wt CNF. The hydrogel sensor was integrated within a 3D printing strip on a diaper, and it offered a vivid color change from light yellow to blue for detecting sarcosine for PCa indication with a detection limit starting from 10 μM. The colorimetric results were semi-quantitatively evaluated by a spectrophotometer offering a linear range of 0-100 μM with R 2 of 0.9901. Furthermore, the increase in CNF content significantly enhanced the sensor's sensitivity toward sarcosine. This sensor could open new avenues for non-invasive screening of prostate cancer in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cyclin D-dependent kinase 4/6 inhibitors palbociclib, ribociclib and abemaciclib, in combination with aromatase inhibitors anastrozole and letrozole or oestrogen receptor degrader fulvestrant, are being assessed as candidates for therapeutic drug monitoring. An ideal bioanalytical method for their determination in patient plasma samples is therefore of high interest, as there is no routine reference method yet available in the clinical practice. In this work, three sample preparation approaches - dispersive liquid-liquid microextraction (DLLME), solid-phase extraction (SPE), and newly developed phospholipid removal (PLR) for LC-MS determination of these six drugs are comprehensively assessed. The methods are validated in the clinically relevant linear ranges with remarkable precision (RSD ≤6.9 %) and accuracy (bias -13.6 - 11.8 %). To compare the procedures in a real-world setting, they are applied on 38 samples from breast cancer patients. The differences between paired results are below 20 % for more than 92 % of the repeats and the RSD is ≤13.1 % between the corresponding results. Statistical comparison of the results reveals excellent overall agreement between the methods (Lin's concordance correlation coefficient ≥0.9969, maximal Bland-Altman bias 6.3 %). DLLME proved to be the most ecologically acceptable method due to the high degree of miniaturisation (AGREEprep score 0.44), PLR enabled very high sample throughput and cost-effectiveness (BAGI 72.5), while SPE showed the best analytical performance (redness score 100). All three methods are suitable for their designated purpose, and the choice of the ideal method can be made based on the scope of application, available funds and equipment and desired ecological footprint., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tajana Silovski reports a relationship with Novartis Pharmaceuticals that includes: speaking and lecture fees. Tajana Silovski reports a relationship with Pfizer Inc that includes: speaking and lecture fees. Tajana Silovski reports a relationship with Elly Lili that includes: speaking and lecture fees. Other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The ecological state of aquatic ecosystems is systematically monitored using various bioindicators in many countries worldwide. In the European Union, freshwater biomonitoring is the central component of the EU Water Framework Directive (WFD, 2000/60/EC) and currently based on morpho-taxonomic methods. DNA metabarcoding is a novel approach to assess the ecological state fast and efficiently based on organismal DNA signatures and thereby support and upscale biomonitoring. However, compliance of metabarcoding with existing morpho-taxonomic methods must be ensured prior to official implementation. Thus, this study, co-designed by research institutions and environmental agencies, explored necessary key parameters and performed method intercalibration for the implementation of metabarcoding into WFD assessments of running waters. We focussed on benthic invertebrates as the most commonly used bioindicators. We analysed 170 invertebrate samples collected as part of the German federal state WFD routine stream biomonitoring, first via microscopic determination and then using metabarcoding. Our goals were to quantify overlap in i) taxonomic composition and ii) ecological status derived with both methods. For this purpose, we established data harmonisation measures to integrate invertebrate metabarcoding data into the official national WFD classification modules considering abundance and presence/absence data. Our results revealed a high (ca. 70 %) overlap of bioindicator taxa found with both methods. Metabarcoding identified significantly more small invertebrate taxa and detected similar proportions of the important bioindicator 'EPT' taxa (mayflies, stoneflies, caddisflies). Despite deviations in some detected bioindicator taxa, the derived ecological status classes were highly correlated between methods, particularly after intercalibration (R 2 = 0.74, Spearman rho = 0.86). Regardless of whether we used abundance or presence/absence data, the resulting stream type classifications showed strong agreement. Thus, our study not only demonstrates the consistency of the methods for the stream types analysed but is also the first to operationalise a path to integration of metabarcoding data into the WFD assessment modules based on formal intercalibration guidelines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Water is a greatly convenient solvent in Raman spectroscopy. However, non-additive effects sometimes make its signal difficult to subtract. To understand these effects, spectra for clusters of model ions, including transition metal complexes and water molecules, were simulated and analyzed. A combined molecular mechanics/quantum mechanics approach was taken to reveal how relative Raman scattering intensities depend on the distance from the solute and the excitation wavelength. The computations indicate a big effect of solute charge; for example, the sodium cation affects Raman scattering by water to a lesser extent than the chlorine anion. The modeling was able to qualitatively reproduce the experimental observation that a solution of a simple salt may work as a baseline better than pure water in many Raman experiments. For absorbing species, an additional scattering boost occurs due to the resonance effect. Simulations thus provide useful insight into solute-solvent interactions and their effects on measured spectra., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: We aim to determine the current treatment patterns and recommendations among physicians for cutaneous lymphomas and to identify the types of skin lymphomas for which existing radiation regimens need improvement., Methods and Materials: A questionnaire from the European Organisation for Research and Treatment of Cancer was distributed to all members of the Cutaneous Lymphoma Tumour Group and Radiation Oncology Scientific Council. This online survey included 13 questions regarding treatment practices for patients with cutaneous lymphoma. The survey was conducted from August 21 to December 18, 2023. Frequency distributions and subgroup comparisons were calculated and analyzed., Results: We collected 51 completed questionnaires from investigators from 19 countries specializing in cutaneous lymphoma treatment. Radiation doses varied significantly (range, 4-60 Gy). Based on the histologic entity, up to one-third of the investigators delivered hypofractionated regimens (range, 14%-35%). Reduced-dose radiation therapy (RT) was considered by 27% to 63% of investigators. Meanwhile, 18 (35%) investigators considered adapting the radiation dose to the response to immunochemotherapy when treating primary cutaneous diffuse large B cell lymphoma-leg type. Regarding total skin electron beam therapy, 91% of centers delivered reduced-dose regimens, and 18% of investigators applied ultrahypofractionated protocols., Conclusions: RT in patients with cutaneous lymphoma is highly heterogeneous among the European Organisation for Research and Treatment of Cancer centers. The development of evidence-based recommendations for RT dose, fractionation, and technique for cutaneous lymphomas is required for optimization and standardization of treatment., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Maintaining or improving health-related quality of life (HRQoL) is as important as extending survival in metastatic colorectal cancer. We report an HRQoL analysis from FRESCO-2 (NCT04322539)., Methods: Patients were randomized to fruquintinib +best supportive care (BSC; n = 461) or placebo +BSC (n = 230). Instruments of EORTC QLQ-C30 and 5-level EQ-5D, and ECOG performance status (PS) were assessed. Changes from baseline scores for QLQ-C30 and EQ-5D were evaluated and minimally important difference thresholds were used to define stable, improved, or deteriorated QoL. Time to deterioration (TTD) was assessed., Results: With fruquintinib versus placebo, baseline QLQ-C30 global health status (GHS) and EQ-5D visual analog scale (VAS) scores were 65.2 versus 64.6 and 67.0 versus 66.6, respectively. Least-squares mean changes from baseline fluctuated throughout treatment. At end of treatment (EOT), mean scores with fruquintinib versus placebo were 53.8 versus 52.3 (QLQ-C30 GHS) and 58.9 versus 58.5 (EQ-5D VAS). For QLQ-C30 GHS, 38.3 % versus 36.5 % of patients receiving fruquintinib versus placebo had stable or improved scores at EOT; median TTD was 2.1 versus 1.8 months (HR, 0.9; 95 % CI, 0.7-1.0). For EQ-5D VAS, 47.9 % versus 42.7 % had stable or improved scores at EOT; median TTD was 2.6 versus 1.9 months (HR, 0.8; 95 % CI, 0.6-0.9). Median TTD to ECOG PS ≥ 2 or death within 30+ /7 days after EOT was 6.6 versus 2.9 months with fruquintinib versus placebo (HR, 0.6; 95 % CI, 0.4-0.7)., Conclusions: Fruquintinib delayed TTD of ECOG PS and did not negatively impact HRQoL versus placebo., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.S. reports the ownership of stock/shares with Amgen; and an advisory council or committee position for and honoraria from Bayer, Servier, Bristol Myers Squibb (BMS), MSB, Glaxosmithkline (GSK), and Takeda. A.D. has received consulting fees from Eisai, Enterome, Guardant Health, HUTCHMED, Natera, Neogenomics, Personalis, Taiho, and Xencor; and grants or funds from BMS, Exelixis, Illumina, Lantheus, Personalis, Taiho, and Takeda. S.L. reports receiving honoraria (as invited speaker) from Roche, Eli Lilly, BMS, Servier, Merck Serono, Pierre Fabre, GSK, and Amgen; consulting fee (advisory boards) from Amgen, Astellas, Bayer, Merck Serono, Eli Lilly, AstraZeneca, Incyte, Daiichi-Sankyo, BMS, Servier, Merck Sharp & Dohme (MSD), GSK, Takeda, Rottapharm, and Beigene; as well as grants or funds (to institution) from Amgen, Merck Serono, Bayer, Roche, Eli Lilly, AstraZeneca, and BMS. R.G.C has received honoraria from AAA-Novartis, Advanz Pharma, Astellas, Bayer, BMS, Boerhinger Ingelheim, Esteve, GSK, HUTCHMED, Ipsen, Merck, Midatech Pharma, MSD, PharmaMar, Pierre Fabre, Roche, and Servier; and has received grants or funds from BMS, and MSD. E.E. has been on an advisory council or committee for, and has received honoraria as well as consulting fees from Agenus, Amgen, Bayer, BMS, Boehringer Ingelheim, Cureteq AG, GSK, Roche, Janssen, Lilly, Medscape, Merck Serono, MSD, Novartis, Organon, Pfizer, Pierre Fabre, Repare Therapeutics Inc., RIN Institute Inc., Sanofi, Seagen International, GmbH, Servier, and Takeda; has received grants or funds (to institution) from AbbVie Deutschland Gmbh & Co KG, Amgen Inc., Array Biopharma Inc., AstraZeneca Pharmaceuticals LP, Bayer, BeiGene, Bioncotech, Therapeutics, S.L., BioNtech RNA Pharmacuticals GMBH, BioNtech Small Molecules GMBH, Boehringer Ingelheim, Boehringer Ingelheim de España S.A., BMS International Corporation, Celgene International Sàrl, Daiichi Sankyo, Debiopharm International S.A., Genentech Inc., Gercor, HalioDX SAS, Roche, HUTCHMED, Iovance Biotherapeutics Inc., Janssen Research & Development, Janssen-Cilag S.A., MedImmune, Menarini, Menarini Ricerche SPA, Merck Health KGAA, Merck, Sharp & Dohme de España S.A., Merus NV, Mirati, Nouscom S.R.L., Novartis Farmacéutica S.A., Pfizer, PharmaMar S.A., Pledpharma A.B., Redx Pharma Plc, Sanofi Aventis Recherche & Développement, Scandion Oncology, Seattle Genetics Inc., Servier, Sotio A.S., Taiho Pharma USA Inc., Wntresearch AB and non-financial conflicts with American Society for Clinical Oncology (ASCO), Leadership Role, Member of the Scientific Program Committee and Developmental Therapeutics-Immunotherapy Track Leader, 2023–2024 term. European Society for Medical Oncology (ESMO), Member of the Scientific Committee 2024. ESMO, Speaker of the ESMO Academy. Sociedad Española de Oncología Médica (SEOM), Coordinator of the SEOM +MIR Section of Residents and Young Assistants. T.Y. declares receiving honoraria from Chugai Pharmaceutical, Takeda, Merck Biopharma, Bayer Yakuhin, Ono Pharmaceutical, and MSD K.K.; a consulting fee from Sumitomo Corp.; and grants or funds from Amgen, BMS, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, FALCO biosystems, Genomedia, Medical & Biological Laboratories, Merus N.V., Molecular Health GmbH, MSD, Nippon Boehringer Ingelheim, Ono Pharmaceutical, Pfizer Japan, Roche Diagnostics, Sanofi, Sysmex, Taiho Pharmaceutical, and Takeda. J.Y. reports consulting fees from HUTCHMED. A.S.B. has received consulting fees from Bayer, Pierre-Fabre, Servier, and Takeda. T.S. reports receiving honoraria from Eli-Lilly, Ono Pharmaceutical, BMS, and Daiichi-Sankyo; as well as grants or funds from Ono Pharmaceutical, BMS, Daiichi-Sankyo, and Shionogi Pharmaceutical. V.R. has received honoraria from Takeda. J.To. reports employment for Masaryk Memorial Cancer Institute, Brno, Czech Republic; receiving honoraria from Amgen, and Merck; and consulting fees from Merck. G.C. has held an advisory council or committee position for Regeneron, Takeda, and BMS; and reports research funding from HUTCHMED, Regeneron, BMS, AstraZeneca, Amgen, Roche, Bayer, Pharmacyclics, Incyte, Dizal Pharma, and Merck. T.P. has been on an advisory council or committee for Takeda, BMS, MSD, and Amgen. Z.Yu., A.G., and L.C. are employees of and hold stocks and shares with Takeda. Z.Ya., W.R.S., and M.K. are employees of and hold stocks and shares with HUTCHMED. J.Ta. reports the ownership of stock/shares with Oniria Therapeutics, Alentis Therapeutics, Pangaea Oncology, and 1TRIALSP; educational collaboration with Medscape Education, PeerView Institute for Medical Education, and Physicians Education Resource (PER); and has received consulting fees from Alentis Therapeutics, AstraZeneca, Aveo Oncology, Boehringer Ingelheim, Cardiff Oncology, CARSgen Therapeutics, Chugai, Daiichi Sankyo, Roche, Genentech Inc., hC Bioscience, Immodulon Therapeutics, Inspirna Inc., Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Ono Pharma USA, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Scandion Oncology, Scorpion Therapeutics, Seattle Genetics, Servier, Sotio Biotech, Taiho, Takeda, and Tolremo Therapeutics. C.E. has been on an advisory council or committee for AbbVie, Amgen, GSK, IGM, Merck, Natera, Pfizer, Seagen, and Taiho. J.A., P.G.A., J.K., A.C.G., have no potential conflicts of interest to report., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The house sparrow (Passer domesticus) is a globally distributed species found in rural, urban and other humanised environments. In Europe, sparrow populations have significantly declined in recent decades, especially in urbanised areas. In the present study, we analysed the impact of urbanization on sparrow body condition, pathogen prevalence, and serum proteome changes. Sparrows were captured in four locations with two different urbanization status (rural/urban). Biometric data, blood samples and oral and cloacal swabs were collected. Rural sparrows exhibited significantly better body condition compared to urban sparrows, with no notable differences between sexes. Haemoparasite prevalence was higher in rural sparrows 70.16 % (87/124) than in urban sparrows 50 % (27/54). No avian influenza virus (AIV) or West Nile virus (WNV) genetic material was found, although one urban sparrow (0.58 %) had antibodies to AIV. Serum proteomics revealed that rural sparrows showed an up-regulation of proteins involved in the metabolism, in contrast to proteins of the immune system and the coagulation system, which were found to be over-represented in urban sparrows. Thus, we documented a worse body condition and immune system activation in urban sparrows in contrast to a more active metabolism and a higher prevalence of avian malaria in rural sparrows, and at least occasional exposure to AIV in urban habitats. This information suggests exposure to urban environments may alter the host-pathogen relationship. Urbanization in combination with exposure to AIV, could modulate their role in viral spread and transmission., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

The effects of climate change, including warming waters, loss of sea ice habitat and the resulting changes in primary production, are inducing shifts in marine communities across the Arctic Ocean. The Arctic marginal ice zone (MIZ) is a highly dynamic ecosystem and is a transition zone between pack ice and the open ocean. It is habitat for a wide range of organisms, including sympagic and pelagic taxa, all of which are affected by the changing physical dynamics of the MIZ. Here we use a multi-marker (18S rRNA V1-2 and COI Leray-XT) approach to investigate eukaryotic biodiversity of the upper water column in this understudied habitat. Environmental DNA (eDNA) was sequenced from seawater samples collected directly beneath the sea ice and at a depth of 5 m, sourced from ice floes representing different ice regimes. To explore the abiotic factors influencing under-ice diversity, we combined satellite-derived environmental data with simultaneous in situ hydrographic measurements. Our analysis identified a range of sympagic and pelagic metazoans, along with primary producers typical of the region, as well as substantial uncharacterised diversity. Alpha diversity indices were higher immediately below the ice, and community composition differed across depths and ice floe stations. We show that the properties of the meltwater stratification in the upper ocean, along with sea ice concentration and distance to the ice edge, significantly shape eukaryotic diversity and community composition. These findings highlight the effectiveness of eDNA metabarcoding for monitoring sub-ice communities and enhance our understanding of eukaryotic biodiversity in the MIZ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Adoption of sustainable maize cropping practices is urgently needed. Synthetic microbial communities (SynComs) made of plant growth-promoting microorganisms (PGPMs), coupled with biochar from residual biomass, offer an environmentally compatible alternative to inorganic fertilizers and may improve soil fertility. This article extends in a two-year field trial with preliminary results obtained in previous pot experiments, monitoring plant physiology, soil biology and chemistry, and kernel metabolomics. Here, we report the synergistic effect of the co-application of biochar, SynComs, and arbuscular mycorrhizal fungi on the soil microbiome, maize growth, and kernel metabolomic profile. SynComs application did not affect the diversity and richness of soil microbial communities; therefore, it posed a low risk of long-term effects on soil microbial ecology. With SynComs and biochar co-application to the soil, the physiology of maize plants was characterized by higher chlorophyll content, ear weight, and kernel weight. The combination of SynComs and biochar also affected the kernel metabolome, resulting in enriched health-beneficial and anti-stress metabolites. Since the preliminary evidence on the environmental and economic impact of these new associations was more favorable than that of conventional fertilizers, it seems reasonable that their large-scale implementation can eventually favor the transition to more sustainable agriculture., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Carbon monoxide (CO) is a valuable compound widely used in industry, and its biological production aligns with the bioeconomy principles. This study introduces a novel perspective by exploring biowaste composting as a potential source of CO production. Using 16S rDNA sequencing, microbial communities within two zones of a compost pile, with low (CO/L, 119 ppm) and high CO concentration (CO/H, 785 ppm), were characterized. The metabolic potential of microbial communities was investigated using PICRUSt2, an advanced tool for functional analysis. Results revealed higher alpha diversity in CO/H samples compared to CO/L, likely influenced by the lower temperature at the CO/H sampling site (50 °C vs. 62 °C in CO/L). Importantly, in the PCoA plots, samples clustered together depending on the sampling site. The microbial community composition was dominated by Bacilli (up to 98.8 % and 55.4 % of CO/L and CO/H samples, respectively). One of the key results was the detection of the Wood-Ljungdahl pathway, a metabolic route for CO production, in nearly all compost samples. This pathway was more abundant in CO/H samples (0.011-0.027 %) compared to CO/L samples (0.000-0.002 %). Moreover, 7 enzymes and 7 genes responsible for CO production and metabolism were detected in compost samples, suggesting that the observed CO formation is likely of biotic origin. The study for the first time underscored the potential of composting as a sustainable method for CO generation and validated PICRUSt2 as a reliable tool for uncovering biotic CO production mechanisms, offering valuable preliminary insights into the functional capabilities of microbial communities., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Karolina Sobieraj reports financial support was provided by European Social Fund. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

DNA immobilization on metal surfaces is widely used for DNA hybridization applications in biotechnology and nanotechnology. Stable DNA binding properties are essential to the functionality and accuracy for these DNA-based applications. We developed an optimized protocol utilizing amine-functionalized surfaces and demonstrated enhanced hybridization efficiency through electrical field assistance. Our approach achieved uniform molecular coverage and improved binding stability compared with conventional thiol-gold chemistry methods. Fluorescence microscopy analysis confirmed successful DNA immobilization and hybridization, with significantly higher signal intensities observed under the optimized conditions. This method provides a promising platform for developing sensitive biosensors and molecular detection systems, offering improved control over the DNA surface density and orientation while maintaining biological functionality.

This study investigates the neural and behavioral mechanisms of tactile perceptual discrimination using fMRI and a set of wrinkled surface stimuli with varying textures. Fifteen female participants were tasked with distinguishing between different surfaces by touch alone. Behavioral results demonstrated variable discriminability across conditions, reflecting the tactile sensitivity of human fingertips. Neural analysis showed varied brain activations tied to the task's difficulty. In the easiest least fine-grained discrimination condition, widespread activations were observed across sensory and integration regions. As task difficulty increased, stronger parietal and frontal lobe involvement reflected higher cognitive demands. In the hardest most fine-grained discrimination condition, activation concentrated in the right frontal lobe, indicating reliance on executive functions. These results highlight the brain's intricate role in processing sensory information during tactile discrimination tasks of varying difficulty. As task difficulty increases, the brain adapts by engaging additional neural resources to meet higher cognitive demands. This research advances our understanding of the psychophysical and neural bases of tactile discrimination acuity, with practical implications for designing materials that enhance tactile feedback., Competing Interests: Declarations. Conflict of interest: The authors declared that they had no conflict of interest with respect to their authorship or the publication of this article., (© 2025. The Author(s).)

Background: Anti-estrogens are widely used to reduce recurrence in breast cancer patients. The side effects often lead to treatment non-adherence and the use of anti-hormonal treatments as primary prevention in women with increased risk of breast cancer is very low. We have conducted breast cancer prevention trials aiming to lower the adverse effects of anti-hormones, but with retained effect. For increased two-way communication and to facilitate effective reporting of adverse events we have developed a smartphone application (app), the KarmApp. The aim of our study was to explore the user frequencies of the different features of the app, and if the use is influenced by age and has changed over time., Methods: Healthy women aged 40-74, attending the Swedish mammography screening program, were invited to participate in trials evaluating risk-reducing medications at different doses and formulations (KARISMA 2, N = 1,440, KARMA Creme, N = 90, and KARISMA Endoxifen, N = 240). After inclusion, participants were given instructions on how to use the app. We retrospectively evaluated the usage frequencies of the KarmApp and its various functions from 2016 to 2024. To explore the age factor attributed to KarmApp usage, age groups were formed and age was also analyzed as a continuous variable, using logistic regression., Results: Of 1,770 participants, 1,646 (93.0%) used the KarmApp and there were 17,065 user interactions, corresponding to 9.6 interactions per person. "Study Activities Overview" was the feature most frequently used. A total of 2,985 adverse events were reported, 2,309 (77.4%) via the KarmApp. The remaining reports were mainly done via phone calls. The younger age, the more likely women were to use the app (p < 0.001), but 75% of women in the highest age group, 60-74 years, used the app. The proportion of users increased over time., Conclusions: A vast majority chose to use the KarmApp and reported side effects via the app. More prevalent use was seen among younger participants and use increased over calendar period. Supported by our data, KarmApp exemplifies the potential of using mobile technologies in clinical trials., Competing Interests: Declarations. Ethics approval and consent to participate: The research was conducted following GCP and in accordance with the World Medical Association Declaration of Helsinki. All participants were included after receiving oral and written study information and giving their written informed consent. The included studies were approved by the regional ethical review board in Stockholm, Sweden; (KARISMA 2 (2016/65–31/2), KARMA Creme (2018/402–31) and KARISMA Endoxifen (2021/037–57)). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Purpose: This study reports on the results from our data-driven approach that identified perturbations in neuroactive ligand-receptor interaction and renin-angiotensin system (RAS) pathways in oncology patients with and without self-reported cancer-related cognitive impairment (CRCI)., Methods: In a sample of oncology patients receiving chemotherapy (n = 1343), the Attentional Function Index (AFI) was used to assess CRCI. Patients were grouped into low (AFI score of < 5) versus high (AFI score of > 7.5) levels of cognitive function. Gene expression analyses were done using RNA-seq (n = 185) and microarray (n = 158) technologies. Pathway impact analysis was used to evaluate for perturbations in biological pathways associated with self-reported CRCI., Results: The combined pathway impact analysis revealed that the neuroactive ligand-receptor interaction and RAS pathways were significantly perturbed between the patients with low versus high AFI scores., Conclusions: Findings from this study suggest that in addition to inflammatory pathways, numerous mechanisms may contribute to the underlying mechanisms for the development and/or persistence of self-reported CRCI., Competing Interests: Declarations. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Committee on Human Research at the University of California, San Francisco. Consent to participate: Written informed consent was obtained from the patients. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Human milk oligosaccharides (HMOs) represent the third most abundant fraction of biomolecules in human milk (HM) and play a crucial role in infant health and development. The unique contributions of HMOs to healthy development of breast-fed infants are assumed to rely on the extraordinary complexity and diversity of HMO isomeric structures, which in turn still cause a huge analytical challenge. Many contemporary analytical methods aiming for more detailed HMO characterization combine ion mobility (IM) with LC-MS for enhanced structural resolution but are typically lacking the robustness necessary for application to HM cohorts with hundreds of samples. To overcome these challenges, we introduce a novel, robust all-ion fragmentation (AIF) LC-ESI-IM-MS method integrating four analytical dimensions: high-resolution LC separation, IM drift time, accurate mass precursor, and fragment ion measurements. This four-dimensional (4D) analytical characterization is sufficient for resolving various HMO structural isomers in an efficient way. Thereby, up to 200 HMO compounds with a maximum degree of polymerization of 13 could be simultaneously identified and relatively quantified. We devised two methods using this 4D analytical approach. One intended for in-depth characterization of multiple known but also novel HMO structures and the second is designed for robust, increased-throughput analyses. With the first approach, five trifucosyl-lacto- N -tetraose isomers (TF-LNTs), four of which were never detected before in HM, as well as additional difucosyl-lacto- N -heaose isomers (DF-LNHs), were revealed and structures fully elucidated by AIF and IM. This exemplifies the potential of our method for in-depth characterization of novel complex HMO structures. Furthermore, the increased-throughput method featuring a shorter LC gradient was applied to real-world HM samples. Here, we could differentiate the HM types I-IV based on a broader range of partly new marker HMOs. We could also derive valuable new insights into variations of multiple and rare HMOs up to DP 11 across lactational stages. Overall, our AIF LC-ESI-IM-MS approach facilitates in-depth monitoring and confident identification of a broad array of distinct and simple to very complex HMOs. We envision this robust AIF LC-ESI-IM-MS approach to advance HMO research by facilitating the characterization of a broad range of HMOs in high numbers of HM samples. This may help to further extend our understanding about HMOs structure-function relationships relevant for infants' healthy development.

of the original article, 'Efficacy of Trastuzumab Deruxtecan in HER2-Expressing Solid Tumors by Enrollment HER2 IHC Status: Post Hoc Analysis of DESTINY-PanTumor02'. Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate, which is a chemotherapy with a linker (deruxtecan) joined to an antibody (trastuzumab). Trastuzumab binds to the human epidermal growth factor receptor 2 (HER2) protein on cancer cells, where it releases the chemotherapy to kill these cells. The DESTINY-PanTumor02 clinical study tested the effectiveness of T-DXd for people with various HER2-expressing cancers and the safety of treatment. Previous results from DESTINY-PanTumor02 showed that T-DXd had antitumor activity, and the greatest effects were seen in people with the highest tumor level of HER2 [defined as immunohistochemistry (IHC) 3+]. In this previous analysis, the HER2 expression was measured at a central laboratory. In clinical practice, HER2 expression will likely be measured at a local laboratory, so understanding whether T-DXd has similar effects regardless of how HER2 expression is measured is important. Here, we looked at the effects of T-DXd based on the HER2 test result used to determine a person's eligibility for the study, which could be measured using a local or central laboratory. In people with IHC 3+ tumors (where HER2 was measured at a local or central laboratory), 51% had a decrease in the size or number of tumors, according to established criteria (referred to as an objective response), while, in people with IHC 2+ tumors, 26% had an objective response. Side effects with T-DXd were consistent with previous studies. These results confirm T-DXd has antitumor effects in HER2-expressing cancers where the HER2 expression is measured by a local or central laboratory., Competing Interests: Declarations. Conflict of Interest: Please see original article for full author disclosures. Ethics Approval, Consent to Participate, Consent to Publish, Availability of Data and Material: Not applicable., (© 2025. The Author(s).)

The binding of carbon dioxide to a transition metal is a complex phenomenon that involves a major redistribution of electron density between the metal center and the triatomic ligand. The chemical reduction of the ligand reveals itself unambiguously by an angular distortion of the CO 2 -molecule as a result of the occupation of an anti-bonding π-orbital and a shift of its antisymmetric stretching vibration, ν 3 , to lower wavenumbers. Here, we generate a carbon dioxide complex of the heavier group-10 metal, platinum, by ultrafast electronic excitation and cleavage of CO 2 from the photolabile oxalate precursor, oxaliplatin, and monitored the ensuing primary dynamics with ultrafast mid-infrared spectroscopy. A neutral and thermally relaxed CO 2 -molecule is detected in the ν 3 -region within 60 ps after impulsive excitation with 266 nm light. Concurrently, an induced absorption peaking at 1717 cm -1 is observed, which is distinctly up-shifted relative to the oxalate stretching bands of the precursor and which resembles the CO stretching absorption of organic ketones. Accompanying density functional theory suggests that the 1717 cm -1 -absorption arises from a Pt-CO 2 product complex featuring a side-on binding mode, which can indeed be regarded as a ketone; specifically, as the metalla-α-lactone, 1-oxa-3-platinacyclopropan-2-one.

This study presents a novel approach to 1 H NMR-based machine learning (ML) models for predicting logD using computer-generated 1 H NMR spectra. Building on our previous work, which integrated experimental 1 H NMR data, this study addresses key limitations associated with experimental measurements, such as sample stability, solvent variability, and extensive processing, by replacing them with fully computational workflows. Benchmarking across various density functional theory (DFT) functionals and basis sets highlighted their limitations, with DFT-based models showing relatively high RMSE values (average CHI logD of 1.12, lowest at 0.96) and extensive computational demands, limiting their usefulness for large-scale predictions. In contrast, models trained on predicted 1 H NMR spectra by NMRshiftDB2 and JEOL JASON achieved RMSE values as low as 0.76, compared to 0.88 for experimental spectra. Further analysis revealed that mixing experimental and predicted spectra did not enhance accuracy, underscoring the advantage of homogeneous datasets. Validation with external datasets confirmed the robustness of our models, showing comparable performance to commercial software like Instant JChem, thus underscoring the reliability of the proposed computational workflow. Additionally, using normalized RMSE (NRMSE) proved essential for consistent model evaluation across datasets with varying data scales. By eliminating the need for experimental input, this workflow offers a widely accessible, computationally efficient pipeline, setting a new standard for ML-driven chemical property predictions without experimental data constraints.

Objective: This meta-analysis aims to evaluate the impact of these two techniques on postoperative pain and quality of life in early-stage NSCLC patients., Methods: A comprehensive literature search was conducted in PubMed, Cochrane Library, Web of Science, and CNKI databases. Randomized controlled trials and cohort studies comparing single-port and three-port VATS lobectomy for early-stage NSCLC were included. The primary outcomes were operating time, postoperative complications, and 24-hour postoperative visual analog scale (VAS) pain scores. The Newcastle-Ottawa Scale (NOS) was used to assess study quality. Meta-analysis was performed using random-effects models, and heterogeneity was assessed using the I² statistic., Results: Fifteen studies involving 3,228 patients (801 in the single-port group and 2427 in the three-port group) were included. The meta-analysis revealed that single-port VATS lobectomy was associated with a longer operating time (SMD: 0.61, 95% CI: 0.29 to 0.93, p < 0.001) compared to the three-port approach. However, single-port VATS demonstrated a lower incidence of postoperative complications (RR: 0.73, 95% CI: 0.59 to 0.90, p < 0.001). There was no significant difference in 24-hour postoperative VAS pain scores between the two groups (SMD: 0.02, 95% CI: -1.41 to 1.45, p > 0.05), although substantial heterogeneity was observed (I² = 98.1%)., Conclusion: This meta-analysis suggests that single-port VATS lobectomy may offer advantages in terms of reduced postoperative complications compared to the three-port approach, despite longer operating times. However, the impact on immediate postoperative pain remains inconclusive due to high heterogeneity among studies., Competing Interests: Declarations. Ethics approval and consent to participate: An ethics statement is not applicable because this study is based exclusively on published literature. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

This study aimed to assess the impact of SARS-CoV-2 therapies on the risk of venous thromboembolism (VTE) and other cardiovascular events. A retrospective, multicenter, observational study included hospitalized patients in Spain due to acute SARS-CoV-2 infection from March 2020 to March 2022. A total of 184,324 hospitalized COVID-19 patients were included, with a mean age of 67.5 (± 16) years of whom 58.4% were male. Among the comorbidities, arterial hypertension was the most common, affecting 52.5% (9618 patients), followed by dyslipidemia in 39.5% (7237 patients), diabetes mellitus in 23.7% (1748 patients), and atrial fibrillation in 10.6% (1948 patients). The overall mortality rate was 17.4% (3183 patients) and 9.9% (1819 patients) required admission to an intensive care unit. Cardiovascular events occurred in 4.08% (748 patients), with VTE occurring in 2.78% (510 patients), myocardial infarction in 0.75% (137 patients), and ischemic stroke in 0.55% (101 patients). Among therapies, beta-lactams were used in 66.7% (12,228 patients), systemic corticosteroids in 56.9% (10,424 patients), and tocilizumab in 11.6% (2128 patients). Multivariate analysis revealed an independent association between VTE and the use of tocilizumab (adjusted OR 2.07; p < 0.01), corticosteroids (adjusted OR 1.44; p = 0.02), and macrolides (adjusted OR 0.58; p < 0.01). None of the therapies were associated with the risk of myocardial infarction or ischemic stroke. In this large national cohort, tocilizumab and corticosteroids exhibited an independent association for the risk of VTE, but not for myocardial infarction or ischemic stroke., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Aims: The absence of direct comparisons between talazoparib plus enzalutamide (TALA+ENZA) and current standard of care hinders evaluating their relative efficacy for first-line (1 L) metastatic castration resistant prostate cancer (mCRPC). This study aimed to compare TALA+ENZA (TALAPRO-2) to abiraterone acetate plus prednisone (AAP) (COU-AA-302) and docetaxel (TAX 327) using a matching-adjusted indirect treatment comparison (MAIC)., Methods: A systematic literature review using the Ovid® interface was performed to identify relevant evidence. Patient-level data from TALAPRO-2 and published data from COU-AA-302 and TAX 327 were used to match populations on clinically relevant confounders. The MAICs were conducted for radiographic progression-free survival (rPFS), overall survival (OS), objective response rate (ORR), along with additional efficacy outcomes., Results: In all-comers, TALA+ENZA statistically significantly prolonged rPFS (HR: 0.256; 95% confidence interval [CI]: 0.183, 0.359; p  < 0.0001), OS (HR: 0.557; 0.405, 0.766; p  = 0.0003), and improved ORR (OR: 3.924; 2.017, 7.634; p  = 0001) versus AAP. In all-comers, TALA+ENZA significantly prolonged OS (HR: 0.446; 0.316, 0.631; p  < 0.0001) and improved ORR (OR: 13.081; 5.757, 29.721; p  < 0.0001) versus docetaxel. All other efficacy outcomes statistically favored TALA+ENZA., Conclusions: These results suggest TALA+ENZA improves clinical outcomes relative to AAP and docetaxel in the 1 L mCRPC all-comers population.

The LCZ4r is a novel toolkit designed to streamline Local Climate Zones (LCZ) classification and Urban Heat Island (UHI) analysis. Built on the open-source R statistical programming platform, the LCZ4r package aims to improve the usability of the LCZ framework for climate and environment researchers. The suite of LCZ4r functions is categorized into general and local functions ( https://bymaxanjos.github.io/LCZ4r/index.html ). General functions enable users to quickly extract LCZ maps for any landmass of the world at different scales, without requiring extensive GIS expertise. They also generate a series of urban canopy parameter maps, such as impervious fractions, albedo, and sky view factor, and calculate LCZ-related area fractions. Local functions require measurement data to perform advanced geostatistical analysis, including time series, thermal anomalies, air temperature interpolation, and UHI intensity. By integrating LCZ data with interpolation techniques, LCZ4r enhances air temperature modeling, capturing well-defined thermal patterns, such as vegetation-dominated areas, that traditional methods often overlook. The openly available and reproducible R-based scripts ensure consistent results and broad applicability, making LCZ4r a valuable tool for researchers studying the relationship between land use-cover and urban climates., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Introduction: The increased risk of tuberculosis (TB) reactivation in solid organ transplant recipients supports the recommendation of screening for latent tuberculosis infection (LTBI). Adherence to available screening tests has not been studied in the kidney transplant (KT) population. We aimed to assess screening compliance within the ATALANTA-DOS population study., Methods: ATALANTA-DOS studied an intervention bundle aimed at preventing infection in KT recipients. We compared LTBI screening rates between the pre-intervention (February 2016 - September 2017) and intervention (February 2018 - September 2019) cohorts and evaluated adherence rates between the interferon-gamma release assay (IGRA) and the tuberculin skin test (TST)., Results: A total of 307 KT recipients were included (155 in the pre-intervention cohort; 148 in the intervention cohort). A systematic assessment of screening compliance by an infectious disease specialist on day +30 post-KT improved LTBI screening adherence (82.6% [114/138] vs 1.3% [2/155]; p-value <0.001). In the intervention cohort, compliance was higher with IGRA (83.3% [52/62]) than with TST (68.1% [49/72]). Two cases of LTBI were detected in the pre-intervention cohort and five in the intervention cohort (4.4% [5/114]). All patients completed LTBI treatment after ruling out active TB. No cases of active TB were identified during follow-up., Conclusions: Systematic evaluation of LTBI screening compliance significantly increased screening completion rates among KT recipients. IGRA-based strategies increased screening compliance, supporting their implementation over TST for LTBI screening among KT recipients. Increased adherence would allow a more targeted and effective treatment of LTBI., (© 2025. Sociedad Española de Quimioterapia. Este es un artículo open access bajo la licencia CC BY-NC 4.0.)

We present a conjugated copolymer designed as a near-infrared (NIR) emitter for organic light-emitting diodes (NIR-OLEDs). The low bandgap donor-acceptor copolymer, comprising a terthiophene derivative (3T) and benzothiadiazole (BT), is end-capped with bulky triphenyalmine (TPA) groups (3TBT-TPA). Compared with the parent homologue capped with simple phenyl rings, 3TBT-TPA shows enhanced solubility in organic solvents with improved photoluminescence quantum yield thanks to a reduced close packing of chains. 3TBT-TPA, used both as neat emitting layer and blended with fluorene-benzothiadiazole (F8BT) host copolymer in a NIR-OLEDs, shows external quantum efficiency up to 0.58%. Additionally, chiral induction is achieved in the F8BT:3TBT-TPA blend film using a commercial chiral dopant, yielding circularly polarized (CP), photoluminescence (PL) and electroluminescence (EL) in the range 500-800 nm with a maximum dissymmetry factor in the range of 10 -2 . This is the first example of CP-NIR EL from a conjugated polymer. This work highlights the potential of TPA-capped strategy for low bandgap copolymers for efficient NIR-OLEDs and opens new perspectives in the use of conjugated polymers in NIR photonic applications., (© 2025 The Author(s). Macromolecular Rapid Communications published by Wiley‐VCH GmbH.)

Accumulating evidence supports an important role of phospholipase D3 (PLD3) in the pathogenesis of Alzheimer's disease (AD), while the actual expression level and distribution of PLD3 remains controversial in AD. Developing specific nanoprobes could be a promising strategy to understand PLD3 better, but there are limited approaches available in this field for a simple, reliable, and biocompatible biosensor. In this work, we report a PLD3-induced fluorescence resonance energy transfer (FRET) nanoprobe utilizing tetrahedral DNA nanostructures (TDNs) for visualizing the fluctuation of PLD3 at organ and subcellular levels in AD. Hydrolysis of PLD3 to a specific nucleotide strand on TDN will turn the FRET probe to an OFF state, which results in changes in fluorescent intensity. Immunofluorescent staining of brain sections proved the reliability of TDN nanoprobe to visualize PLD3 and the upregulation of PLD3 was observed in AD mice. Subsequent application of the nanoprobe uncovered PLD3 in the heart tissue of AD mice for the first time. Further investigations on the cellular level revealed a good colocalization of TDN nanoprobes with lysosomes in normal neurons, while their fluorescent signal overlaps better with mitochondria than lysosomes in AD neurons. Our finding provides not only insights into PLD3 but also an inspiring application of TDNs in the mechanism research of AD at multiple levels.

Natural photonic structures allow us to reveal and mold the thermophoretic effect at the nanoscale within condensed matter systems. In this paper, for the first time, holography has been exploited to disclose conditions that determine the strength and dynamics of the thermophoretic effect. We experimentally revealed the link between geometry and nano-corrugation of biological structures that shapes the power of thermophoresis. The presented study opens enormous possibilities for harnessing the thermophoretic effect in various bioinspired sensing applications, uniquely merging the fields of photonics and mechanics., (© 2025 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Silicate glasses are not only used for everyday items such as windows or drinking glasses. By altering their composition, one can adjust their properties to allow them to become degradable and help to regenerate bone. Here, we investigate how compositional changes from conventional soda lime silicate glasses to low-silica content compositions affect their structure and properties. Results show that silicate network polymerisation, known as network connectivity, controls many properties, including viscosity, which is relevant for processing, and reactivity in aqueous environments. Correlating our data with in vivo results from the literature, we show how changes in silicate network connectivity as represented by their modifier content and non-bridging oxygen concentration, allow us to turn bioinert soda lime silicate glasses into bioactive materials to enhance bone formation.

A sustainable, general and scalable electrochemical protocol for direct access to 3-(acylamidoalkyl)-2,1-benzisoxazoles by cathodic reduction of widely accessible nitro arenes is established. The method is characterised by a simple undivided set-up under constant current conditions, inexpensive and reusable carbon-based electrodes, and environmentally benign reaction conditions. The versatility of the developed protocol is demonstrated on 39 highly diverse examples with up to 81% yield. A 50-fold scale-up electrolysis highlights its relevance for preparative applications.

Interactions between vehicle-pedestrian at intersections often lead to safety-critical situations. This study aims to model the crash avoidance behaviors of vehicles during interactions with pedestrians in near-miss scenarios, contributing to the development of collision avoidance systems and safety-aware traffic simulations. Unmanned aerial vehicles were leveraged to collect high-resolution trajectory data of vehicle-pedestrian at urban intersections. A new surrogate safety measure, curvilinear time-to-collision (CurvTTC), was employed to identify vehicle-pedestrian near-miss scenarios. CurvTTC takes into account the curved trajectories of road users instead of assuming straight-line future trajectories, making it particularly suitable for safety analysis at intersections, where turning vehicles usually follow curved paths. An effective algorithm considering predicted trajectories and collision types was designed to compute CurvTTC. When CurvTTC was applied to capture vehicle-pedestrian conflicts at intersections, it demonstrated superior performance in identifying risks more accurately compared to other surrogate safety measures, emphasizing the importance of considering the curved trajectories of road users. Further, a novel deep deterministic policy gradient based on the Mamba network (Mamba-DDPG) approach was used to model vehicles' crash avoidance behaviors during the vehicle-pedestrian conflicts captured. Results revealed that the Mamba-DDPG approach effectively learned the vehicle behaviors sequentially in both lateral and longitudinal dimensions during near-miss scenarios with pedestrians. The Mamba-DDPG approach achieved superior predictive accuracy by utilizing Mamba's dynamic data reweighting, which prioritizes critical states. This resulted in better performance compared to both the standard DDPG and the Transformer-enhanced DDPG (Transformer-DDPG) methods. The Mamba-DDPG approach was employed to reconstruct evasive trajectories of vehicles when approaching pedestrians and its effectiveness in capturing the underlying policy of crash avoidance behaviors was validated., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Background: The Hopkins Verbal Learning Test-Revised (HVLT-R) is widely used for assessing episodic memory. In this study, we evaluated the HVLT-R with Semantic Cues (HVLT-R-SC), an adapted version incorporating semantic cues to improve diagnostic utility. The assessment was conducted in a Spanish cohort comprising cognitively unimpaired controls, individuals with multi-domain amnestic mild cognitive impairment (md-aMCI), and early Alzheimer's disease (AD). Methods: 684 participants (333 controls, 141 md-aMCI, and 210 early AD) completed the HVLT-R-SC. Effect sizes were calculated to quantify group differences, while Cronbach's alpha was used to assess the test's reliability. Receiver Operating Characteristic curve analysis was performed to assess discriminatory power, with the Area Under the Curve (AUC) summarizing classification accuracy. Sensitivity, specificity, and efficacy percentages were reported, with optimized cutoff points determined. Odds ratios quantified the association between HVLT-R-SC performance and diagnostic group classifications. Results: Significant differences were observed across all HVLT-R-SC indices among the groups. Total Delayed Recall with and without Semantic Cues exhibited the largest effect size (η 2 = 0.69), with Total Delayed Recall with Semantic Cues demonstrating the highest diagnostic accuracy (AUC = 0.90 for differentiating md-aMCI from controls and 0.99 for distinguishing early AD from controls). Optimal cutoffs for Total Delayed Recall with Semantic Cues were 5 words for md-aMCI (sensitivity = 74%, specificity = 90%, efficacy = 85.44%) and 4 words for early AD (sensitivity = 93%, specificity = 97%, efficacy = 95.21%). Significant associations were observed between HVLT-R-SC performance and diagnostic classification, with an odds ratio of 26.04 for md-aMCI and 362.50 for early AD. Internal consistency was excellent (Cronbach's alpha = 0.95), indicating strong reliability of the HVLT-R-SC. Conclusions: The HVLT-R-SC demonstrated strong reliability and excellent diagnostic performance in identifying memory impairments. The inclusion of semantic cues improved diagnostic accuracy, provided clinically actionable cutoff points, and enhanced the test's utility, particularly for detecting md-aMCI and early AD.

Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genodermatosis characterized by severe cutaneous and mucosal fragility, and frequently complicated by multifactorial chronic anemia that responds poorly to conventional therapies. This cross-sectional study investigates the factors contributing to anemia in RDEB by analyzing a representative cohort, that was stratified by disease severity, anemia and iron status, to examine their hematological parameters, cytokine profile and erythropoietin (EPO)-erythroferrone (ERFE)-hepcidin axis. Anemia was present in 50% of the cohort. Hemoglobin levels showed a strong negative correlation with the percentage of body surface area affected and C-reactive protein levels (CRP), identifying these as anemia risk factors in RDEB. Moderate-severe inflammation (CRP≥15mg/L) was observed in all anemics, but no specific cytokine profile was linked with anemia risk due to variability in IL6, IL1β, IL10, TNF, and IFN-γ levels. The regulation of the EPO-ERFE-hepcidin axis showed discrepancies with the patterns expected based on patients' anemia severity and iron status. According to reticulocyte production index, an inadequate bone marrow response was observed in 90% of anemics, irrespective of EPO levels. Patients with functional or true iron deficiency had higher ERFE levels, though ERFE showed no consistent correlation with EPO and was elevated in both anemic and non-anemic patients. Elevated hepcidin was primarily linked to the highest ferritin levels mostly in patients with a history of iron infusions and/or transfusions. These findings highlight the need for personalized, targeted approaches that address the complex interplay between inflammation and iron dysregulation, to improve anemia management in RDEB and other chronic inflammatory conditions., (Copyright © 2025 American Society of Hematology.)

Objectives: To evaluate the effect of genetic variant status on sotatercept efficacy and effect of sotatercept treatment on biomarkers in pulmonary arterial hypertension Methods: PULSAR (NCT03496207) was a phase 2, randomized, controlled study of sotatercept vs placebo added to background therapy for pulmonary arterial hypertension. Participants had DNA sequencing done at baseline to detect genetic variants in disease-associated genes ( ACVRL1, BMPR2, CAV1, EIF2AK4, ENG, KCNA3, KCNK3 , and SMAD9 ). Safety (adverse events) and efficacy (pulmonary vascular resistance, 6-minute walk distance) were assessed by variant status and treatment at 24 weeks. Serum levels of BMPR2 mRNA and N-terminal pro-hormone B-type natriuretic peptide were assessed at baseline and 24 weeks by treatment and variant status. Analysis of covariance was used to compare the change from baseline by treatment and variant status., Results: Of 76 participants included, 25 had pathogenic variants detected (23 BMPR2 ; 2 other) and 51 had no variants or variants of uncertain significance. BMPR2 mutation carriers were younger and more frequently on triple therapy but had less severe clinical characteristics at baseline. Changes at 24 weeks in pulmonary vascular resistance and 6-minute walk distance did not differ by variant status. BMPR2 gene expression varied less than twofold from baseline over time, irrespective of treatment or variant status. The adverse events profile was generally consistent with that seen in the parent PULSAR study., Conclusions: These results suggest consistent safety and clinical efficacy of sotatercept for treatment of pulmonary arterial hypertension, irrespective of BMPR2 variant status. Clinical trial registration available at www., Clinicaltrials: gov, ID: NCT03496207.

The presence of phytate in broiler diets restricts phosphorus availability, a crucial nutrient for muscle and bone development, leading to reduced performance. To alleviate this issue, exogenous enzymes such as phytase are introduced; however, the wide variety of phytases available on the market and their effectiveness are not yet fully understood. The objective of this study was to evaluate the phosphorus equivalence of commercial phytase in broiler diets, using the standard curve, and its effects on performance, bone mineralization, intestinal histological integrity, liver relative weight, and total alkaline phosphatase in the initial phase (1 to 21 days) of broiler. We used 2,500 male broiler chickens, with an initial weight of 44 g, distributed in a completely randomized design with 10 treatments and 10 replications of 25 birds per experimental unit. The diets were formulated to meet the nutritional requirements of the birds, except for the available phosphorus (Pd) and calcium content. The treatments were divided as follows: T1-Control (CT) with 0.18% Pd; T2-CT + 0.07% aP; T3-CT + 0.14% aP; T4-CT + 0.21% aP; T5-CT + phytase 1; T6-CT + phytase 2; T7-CT + phytase 3; T8-CT + phytase 4; T9-CT + phytase 5; and T10-CT + phytase 6. For enzymatic standardization, 500 FTU/kg (Phytase Units) of each enzyme were used. Animals subjected to the highest levels of P (T2, T3, and T4) and with the addition of commercial phytases (T5, T6, T7, T8, T9, and T10) had better performance and bone mineralization results when compared to T1-CT. All phytases evaluated improved final live weight, weight gain, feed conversion, and ash and phosphorus content in the tibia and intestinal development compared to CT. Supplementing broiler diets with commercial phytases enhances performance, bone mineralization, and jejunal development from 1 to 21 days.The average phosphorus availability from phytic acid in these phytases was 0.154%. The comparison of the six commercial phytases in diets for broiler chickens, using the standard curve and supplementation with 25 g/t of commercial phytase, showed similar results, promoting improvements in performance, bone mineralization, and jejunal development., Competing Interests: Declarations. Conflicts of interest: The authors declare no conflicts of interest., (© 2025. The Author(s), under exclusive licence to Springer Nature B.V.)

Zwitterionic hydrogel based on a dual-crosslinked network of pluronic F-127 dimethacrylate (PLU-DMA) and a terpolymer, poly(sulfobetaine methacrylate)-co-methacrylic acid-co-N-methacryloyloxyethyl tyrosine methylester) (PSBMM) was prepared and successfully applied as an enzyme-based colorimetric sensor of urea on diaper. The prepared hydrogel possessed good mechanical property while preserving its swelling capability. The urease-incorporated hydrogel exhibited a vivid color change from yellow to orange and red, enabling semi-qualitative detection of urea via naked eye in a linear range of 0-0.7 M covering a cut-off value of 0.3 M, which allow for distinguishing between the chronic kidney-prone patients from the normal individuals. The hydrogel was found to be non-toxic and demonstrated effective enzyme preservation by maintaining more than 80% of urease activity up to 14 days. This hydrogel-based urea sensor was also validated by laser desorption ionization mass spectrometry (LDI-MS) with satisfactory results. This platform demonstrated its potential integration on diaper for real-time screening of urea in the point-of-care diagnostics of chronic kidney disease (CKD)., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Immobilization of enzymes on (nano)porous metal carriers provides the foundation for an advanced design of bioelectrodes suitable for catalysis and sensing. However, interactions upon adsorption are still poorly understood, and so the efficient coupling of the enzymes to the electrode surface remains one of the major challenges. Here, we present a comprehensive study of the immobilization behavior of Aerococcus viridans l-lactate oxidase (LOx) on nanoporous gold (npAu) in dependence of electrode modification with differently charged self-assembled monolayers (SAMs). The highest activity (up to 14 U/g) and electrocatalytic response (sensitivity of 3.9 μA mM -1 ) were observed for a sulfonate-terminated SAM. This is contrary to enzyme behavior on conventional polymer carriers, and thus, the effect is specific to the metal electrodes. We propose the capture of the negatively charged LOx in a dense counterion layer in close proximity to the strongly negatively charged gold surface. Adsorption on positively charged amine-terminated SAMs resulted in a similar immobilization yield but gave much lower activity (4-fold). Importantly, the effect of the sulfonate SAM was strongly dependent on the npAu electrode pore size: the highest LOx activity (in U/cm 2 ) was found with pores (diameter of ∼170 nm) supposedly large enough to facilitate enzyme diffusion into the porous structure during immobilization. Electrochemical sensing of H 2 O 2 produced by the LOx reaction showed a 2.5-fold higher sensitivity for l-lactate on the negatively charged surface. Lixiviation studies supported the proposed layer capture and revealed a faster decline in the electrode activity with sulfonate surface modification. Collectively, the present study reveals enhanced activity of LOx on sulfonate-charged gold surfaces and a strong pore size dependence. These findings deepen the understanding of the immobilization behavior of LOx on charged nanoporous metals and have importance for the advanced design of enzyme electrodes.

Silver-based dressings are used to reduce infection risk and optimize conditions for wound healing. They are widely used in the management of burns and other complex wounds. However, reports of elevated serum silver and concern over systemic toxicity have meant that their use in young children has been questioned. The aim of the current study was to map the literature relating to the use of silver-based dressings in children under 1 year of age. A systematic scoping review was conducted according to the methodology described by the Joanna Briggs Institute. Sources were identified from major medical databases as well as the gray literature. Inclusion criteria were the use of silver-based dressing in children under 1 year of age. Outcomes of interest were complications or adverse events attributed to silver-based dressings and elevated serum silver levels. A total of 599 sources were identified through the search strategy, with 110 included for review. Complications were described in 31 sources, with the most frequent being wound infection. No cases of argyria, kernicterus, or methemoglobinemia were reported. Six sources documented elevated serum silver levels in infants but none reported adverse events related to this. On the basis of current evidence, we suggest reserving silver dressings in infants under 1 for wounds that are at high risk of infection. Wound area and duration of treatment should be considered when assessing the risk of systemic absorption of silver. Standardized data collection and recording of complications and adverse events is recommended to better inform future clinical decision-making., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: The rapid plasma reagin (RPR) test, a traditional method for diagnosing syphilis and evaluating treatment efficacy, relies on subjective interpretation and requires high technical proficiency. This study aimed to develop and validate a user-friendly RPR-artificial intelligence (AI) interpretative tool., Methods: A dataset comprising 600 images of photographed RPR cards from 276 negative and 223 positive RPR samples was used for model development. The reference result was based on consistent interpretations by at least two out of three experienced laboratory personnel. Then an interpretative model was developed using deep learning algorithms and loaded into smartphones for on-site interpretation at two clinical centers from October 2023 to April 2024., Results: The model demonstrated an accuracy of 82·67% (95% CI 71·82%-90·09%) for reactive circles and 84·44% (95% CI 69·94%-93·01%) for non-reactive circles. In the field study, 669 specimens showed a sensitivity of 94·85% (95% CI 89·29%-97·73%), specificity of 91·56% (95% CI 88·78%-93·71%), and concordance of 92·23% (95% CI 89·87%-94·09%). The positive predictive value was 74·14% (95% CI 66·86%-80·33%) and negative predictive value was 98.59% (95% CI 96·98%-99·38%)., Conclusions: The tool assists in RPR interpretation standardization, enabling data traceability, and quality control for remote and underdeveloped areas., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Ltd.)

Pituitary abscesses are rare entities that may occur in a previously healthy gland or in the setting of a pituitary tumor. Only eleven cases of abscesses associated with craniopharyngioma have been reported in the literature. The etiology is unknown and the diagnosis is difficult because there are no specific clinical or radiologic features that allow us to suspect the synchrony of both entities before surgery. Intraoperative findings and culture are the only definitive signs to confirm this association. Here we present the first surgical video showing this unique association and highlighting the technical pearls of the procedure. In a 9-year-old boy, we performed a transphenoidal approach to resect the tumor and saw pus during surgery. Pathology revealed a papillary craniopharyngioma, with microbiology showing Staphylococcus aureus. The tumor resection resulted in ophthalmologic improvement but pituitary insufficiency. A brief review of the literature is presented., (Copyright © 2025. Published by Elsevier España, S.L.U.)

Antecedents and Objective: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality. Traditional factors strongly associated with poor outcome are neurological condition and the amount of bleeding. Inflammation is considered a relevant mechanism of brain injury after aSAH. This study aims to investigate the potential role of new laboratory indexes related to inflammation for predicting the prognosis of aSAH patients, complementing established prognostic models., Materials and Methods: We conducted a retrospective observational study including adults admitted for aSAH at a single neurosurgery center from 2002 to 2023. Demographic data, clinical parameters, and blood test results at admission were collected. The main outcome variable was Glasgow Outcome Scale (GOS) six month post-bleeding. A second outcome variable was in-hospital mortality. Univariable analyses were performed to identify new laboratory predictors of poor prognosis. The independent association with outcome was evaluated after adjustment of traditional risk factors by logistic regression analysis. The additional value of new laboratory predictors was determined by comparison of the area under the receiver operating curve (AUROC)., Results: Among 542 patients with aSAH, 417 met inclusion criteria (age >18 years old and complete laboratory test available upon admission with aSAH confirmed by CT angiography (CTA) or digital subtraction angiography (DSA)). Elevated glucose/potassium ratio (GKR) in the first blood test at admission was significantly associated with unfavorable outcome and in-hospital mortality according to univariate analysis. The GKR was significantly associated with a worse final prognosis (OR 1.033, 95% CI 1.008-1.040) adjusted for age, WFNS and Fisher scales, history of diabetes mellitus and kidney disease, and prior use of diuretics, oral antidiabetic medications and insulin. Additionally, the inclusion of the GKR improved the predictive accuracy of a prognostic model compared to a model including only clinical and radiological data. The neutrophil-lymphocyte ratio (NLR) was not significantly different between subgroups of patients regarding their outcome., Conclusion: GKR measured in the first 24 h after aSAH may improve the discrimination of patients with higher risk of experiencing poor outcome at six month after the bleeding., (Copyright © 2025. Published by Elsevier España, S.L.U.)

This study examines the relationship between political contributions and Environmental, Social, and Governance (ESG) measures in US firms. Using data from LSEG Workspace (2010-2023), we implement GMM-SYS estimation to analyze the impact of corporate political donations on ESG metrics. Our results show that political contributions increase the ESG Score (through the E and G pillars) but also cause more ESG controversies for the firm. This suggests that firms may resort to political donations to obtain artificially high ESG Scores, which however do not translate into fewer ESG controversies. This work makes three key contributions. First, it bridges a gap in the literature by empirically examining the interplay between political donations and ESG performance across the three ESG pillars. Second, it highlights the dual role of political contributions: enhancing ESG scores while exacerbating ESG controversies, thus raising concerns about greenwashing practices. Lastly, our findings emphasize the importance of strengthening regulatory oversight to ensure that political activities do not undermine corporate sustainability goals., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare. All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report. We certify that the submission is original work and is not under review at any other publication., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Background: Dementia-friendly hospitals are increasingly discussed in healthcare, politics, research and society as a way to improve hospital stays for people with dementia. However, the perspective of people with dementia is often underrepresented, and current definitions and concepts are primarily based on the expertise of healthcare professionals., Objectives: To identify characteristics of a dementia-friendly hospital from the perspective of people with dementia., Methods: A qualitative design embedded in a case study was used. We conducted 15 semi-structured interviews with people with dementia during their hospital stay. The interviews were analysed using reflexive thematic analysis with an inductive approach. In our study, we adopted a participatory approach and actively involved people with dementia and other stakeholders in the development of the interview guide and in the data analysis., Results: The participants expect more than what's necessary from a dementia-friendly hospital, as presented by eight characteristics identified: (i) The most important thing is how we treat each other; (ii) Someone cares about ME; (iii) No hully gully! I want professional care; (iv) Focusing on my goals; (v) LOOK! I've still got capabilities; (vi) Skipping Groundhog Day; (vii) A bit of both: mingle and single, and (viii) Recognising what relatives mean to me., Conclusion: Our results highlight the importance of involving people with dementia in the development of dementia-friendly hospitals as only they have the lived experience and a different perspective from that of healthcare professionals., (© The Author(s) 2025. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Research on the distribution and association of depression with tobacco consumption among young population is commonly prioritised in India, while studies on tobacco use among middle-aged (45-59 years) and elderly (≥ 60 years) adults are noticeably lacking. Thus, we conducted this study with the objectives of estimating the prevalence, distribution and determining the association of depression and tobacco consumption among middle-aged and elderly Indian population; overall and stratified into age group, gender, and geographical location., Methods: Using dataset from Longitudinal Aging Study in India (LASI), a bivariate analysis was conducted among middle-aged (45-59 years) and elderly (≥ 60 years) Indians to estimate the prevalence of depression and tobacco consumption. States and Union Territories were categorised as low, medium, and high as per prevalence of depression and tobacco consumption, and spatial distribution maps were created. To reduce the confounding effects of demographic & socioeconomic and health-related & behavioural covariates; propensity score matching (PSM) was conducted. Nested multilevel regression modelling was employed to explore the association between depression (outcome variable) and tobacco consumption (explanatory variable) using STATA version 17. The p value < 0.05 was considered statistically significant., Results: Overall, 36.78% (36.03-37.55%) participants documented using any form of tobacco; with higher consumption of smokeless tobacco (SLT) (19.88%) than smoking (SM) (13.92%). The overall prevalence of depression was 7.62% irrespective of tobacco consumption, and 8.51% among participants consuming any form of tobacco. Mizoram had the highest consumption of tobacco in any form (78.21%), whereas Madhya Pradesh recorded the highest (14.62%) depression prevalence. Bihar, Uttar Pradesh, West Bengal, and Uttarakhand had both high prevalence of depression and any form of tobacco consumption. The average estimated treatment effect (ATE) indicated a positive association both between depression and any form of tobacco consumption (p value = 0.001) and with smokeless tobacco (p value = 0.001) consumption. Participants ever consuming any form of tobacco had 28% higher odds (aOR-1.28 (1.18-1.38). The odds of having depression were higher among females (aOR = 1.28 (1.17-1.41); richest (aOR-1.48 (1.32-1.65); living alone (aOR = 1.14 (1.01-1.33). Participants with comorbidity (aOR = 1.20 (1.10-1.30) and multimorbidity (aOR = 1.24 (1.13-1.36)) had higher odds of depression., Conclusion: The study has established significant positive association between depression and tobacco consumption stratified into gender and age group. Prioritisation of mental health disorders like depression and tobacco prevention and cessation programmes must be implemented with focusing on females and the middle-aged population with community awareness and intersectoral collaborative effort irrespective of subnational-variations., Competing Interests: Declarations. Ethical Approval: The dataset of LASI is available in the public domain and can be retrieved upon data request, therefore the ethical approval for the present study was not deemed necessary. However, the ethical approval to conduct LASI was given by the Indian Council of Medical Research’s (ICMR) Central Ethics Committee on Human Research (CECHR) as per the Helsinki declaration [20]. Consent to participate: Informed consent was obtained from the participants during the survey. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Activated phosphoinositide 3-kinase (PI3K) delta syndrome (APDS) is an ultrarare genetic disorder characterized by overlapping immunodeficiency and immune dysregulation. Its diagnosis poses challenges owing to its clinical similarities with other inborn errors of immunity (IEIs), compounded by the absence of targeted treatments in today's medical landscape. The standard approach involves symptom management, reducing infection through immunoglobulin replacement therapy and prophylactic antimicrobials, and treating immune dysregulation with immunomodulators. This approach considerably hampers effective management of APDS, as the diverse nature of the disease necessitates a personalized strategy, in which the advantages and risks of immunosuppression are weighed against the potential for recurrent infections and lymphoproliferative complications. To address these challenges, a group of Spanish experts in the management of IEIs, including APDS, collaborated to develop Delphi-based consensus recommendations. The primary goal of the initiative was to offer guidance on various aspects of this complex disease, marking a pioneering effort in Europe. The consensus aims to facilitate early diagnosis and provide clues for individual patient-based decisions that could favor balanced risk-benefit estimations for treatment.

Plants cope with the environment by displaying large phenotypic variation. Two spectra of global plant form and function have been identified: a size spectrum from small to tall species with increasing stem tissue density, leaf size, and seed mass; a leaf economics spectrum reflecting slow to fast returns on investments in leaf nutrients and carbon. When species assemble to communities it is assumed that these spectra are filtered by the environment to produce community level functional composition. It is unknown what are the main drivers for community functional composition in a large area such as Amazonia. We use 13 functional traits, including wood density, seed mass, leaf characteristics, breeding system, nectar production, fruit type, and root characteristics of 812 tree genera (5211 species), and find that they describe two main axes found at the global scale. At community level, the first axis captures not only the 'fast-slow spectrum', but also most size-related traits. Climate and disturbance explain a minor part of this variance compared to soil fertility. Forests on poor soils differ largely in terms of trait values from those on rich soils. Trait composition and soil fertility exert a strong influence on forest functioning: biomass and relative biomass production., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Data on the safety profiles and clinical outcomes of patients with solid tumors and cardiac metastasis treated with immune checkpoint inhibitors (ICIs) are limited., Methods: This is an international multicenter retrospective study of patients with cancer and cardiac metastasis at baseline. Patients who had received ≥1 dose of ICI were included. Treatment-related adverse events (trAEs) were graded per Common Terminology Criteria for Adverse Event V.5.0. Objective response rates (ORR) were evaluated by Response Evaluation Criteria in Solid Tumors V.1.1 when available. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method., Results: Among 110 pts, median age at ICI initiation was 65 (IQR: 59-75). Median follow-up time since ICI initiation was 36 (95% CI: 26 to 51) months. Melanoma (38%, n=42) and non-small cell lung cancer (24%, n=26) were the most common. 68 (62%) patients received ICIs as first-line, and 29 (26%) patients were treated with combination anti-programmed death-1 and anti-cytotoxic T-lymphocyte antigen 4. The most common location of cardiac metastasis was in the atria (37%, n=41) and ventricles (35%, n=39). 15 patients (13.6%) had bilateral cardiac/pericardial metastasis, 44 (40%) had left-sided, and 43 (39.8%) had right-sided. At ICI initiation, 21% (n=23) had a cardiac thrombus. Cardiology referrals and cardiac MRIs at the time of cancer diagnosis were completed on 58 (53%) and 52 (47%) patients, respectively. Cardiac events occurred in 40 (36%) patients, including arrhythmias (n=14, 13%), arterial/venous emboli (n=4, 3.6%), and cardiac tamponade (n=3, 2.7%). 53 (47%) patients developed trAEs; most common were colitis/diarrhea (n=16, 15%), dermatitis (n=13, 12%), and hepatitis (n=9, 8.2%). ICI-related major cardiac trAEs occurred in 2 (1.8%) patients. 22 patients (20%) developed grade ≥3 trAE. Patients with multiple cardiac metastases had significantly lower responses to ICI-based regimens compared with patients with single cardiac metastasis (11% vs 63%, p=0.02). For melanoma, ORR, median PFS, and median OS were 38%, 9.0 months, and 28.9 months, respectively. 83% of patients with melanoma had concordant responses in overall disease burden and cardiac disease. 91 patients discontinued ICIs, and the main reason was progression or death in 55 (49%) patients., Conclusions: Among patients with pre-existing cardiac metastasis, ICIs demonstrated meaningful clinical efficacy with no increase in safety signals. Most patients had concordant responses in the overall disease burden and cardiac mass. Multidisciplinary teams are crucial for the appropriate management of patients with cardiac metastasis., Competing Interests: Competing interests: AHN receives honoraria from OncLive, TEMPUS, and Korean Society for Medical Oncology. Consulting fees: Guidepoint Global. EHY: Research funding/grants from CSL Behring, Boehringer Ingelheim and Eli and Lilly, Bristol Myers Squibb, and Amgen. Consulting fees from Pfizer, Xencor. RRM: consultant/advisor: AstraZeneca, Ambrx, Aveo, Bayer, Blue Earth Diagnostics, Bristol-Myers Squibb, Calithera, Caris, Dendreon, Exelixis, Eisai, Johnson & Johnson, Lilly, Merck, Myovant, Novartis, Pfizer, Sanofi, Seagen, Sorrento, Telix, Tempus. AD: Ad Board/Consulting for: SeaGen, Astra Zeneca, Merck, EMD Serono, Exelixis, Eli Lilly, Infinity, Roche.DJP: Lecture fees: Bayer Healthcare, Astra Zeneca, EISAI, Bristol Myers-Squibb, Roche, Ipsen; Travel expenses: Bristol Myers-Squibb, Roche, Bayer Healthcare; Consulting fees: Mina Therapeutics, Boehringer Ingelheim, Ewopharma, EISAI, Ipsen, Roche, H3B, Astra Zeneca, DaVolterra, Mursla, Avammune Therapeutics, LiFT Biosciences, Exact Sciences; Research funding (to institution): MSD, BMS, GSK.Alessio Cortellini received grants for consultancies/advisory boards: BMS, MSD, OncoC4, IQVIA, Roche, GSK, AstraZeneca, Access Infinity, Ardelis Health and REGENERON. He also received speaker fees from AstraZeneca, EISAI, MSD, SANOFI/REGENERON and Pierre-Fabre. KN receives honorarium from Pfizer, Eisai, AstraZeneca, Eli Lilly, Takeda, Chugai, Fuji Film Pharma, PDR pharma, MSD, Boehringer Ingelheim, Ono, Daiichi-Sankyo, Bayer, Jansen, and Sanofi. Advisory board: Eisai, AstraZeneca, Sanofi, Genmab, Gliad, OncXerna, Takeda, Novartis, MSD, Henlius. Research support (to institution): MSD, Daiichi-Sankyo, Merck Biopharma, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seattle Genetics, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, Haihe. Principal investigator: MSD, Daiichi-Sankyo, AstraZeneca, Taiho, Merck Biopharma Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seattle Genetics, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, Haihe. SG received honoraria from BMS, MSD, Sanofi, Novartis, Medison, Merck Serono. JE receives honoraria from Roche, AstraZeneca, and BMS. Consulting: Roche. Expert testimony: Roche. Travel expenses: MSD. SD: consultancy role with AstraZeneca, Gilead Sciences, Pfizer, Novartis, Myocardial Solutions, Eli Lilly none relevant to this manuscript. Funding: None. TKC reports: Institutional and/or personal, paid and/or unpaid support for research, advisory boards, consultancy, and/or honoraria past 5 years, ongoing or not, from: Alkermes, AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers-Squibb, Calithera, Circle Pharma, Deciphera Pharmaceuticals, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, Gilead, HiberCell, IQVA, Infinity, Ipsen, Jansen, Kanaph, Lilly, Merck, Nikang, Neomorph, Nuscan/PrecedeBio, Novartis, Oncohost, Pfizer, Roche, Sanofi/Aventis, Scholar Rock, Surface Oncology, Takeda, Tempest, Up-To-Date, CME events (Peerview, OncLive, MJH, CCO and others), outside the submitted work; Institutional patents filed on molecular alterations and immunotherapy response/toxicity, and ctDNA; Equity: Tempest, Pionyr, Osel, Precede Bio, CureResponse, InnDura Therapeutics, Primium; Committees: NCCN, GU Steering Committee, ASCO/ESMO, ACCRU, KidneyCan; Medical writing and editorial assistance support may have been funded by Communications companies in part; No speaker’s bureau; Mentored several non-US citizens on research projects with potential funding (in part) from non-US sources/Foreign Components; The institution (Dana-Farber Cancer Institute) may have received additional independent funding from drug companies or/and royalties potentially involved in research around the subject matter; TKC is supported in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE (2P50CA101942-16) and Program 5P30CA006516-56, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, Pan Mass Challenge, Hinda and Arthur Marcus Fund and Loker Pinard Funds for Kidney Cancer Research at DFCI. ARN reports Funding to Institution for Trials he is PI on: Loxo@Lilly, Surface Oncology, ADC Therapeutics, IGM Biosciences, EMD Serono, Aravive, Nikang Therapeutics, Inspirna, Exelexis, Revolution Medicine, Jacobio, Pionyr, Jazz Pharmaceuticals, NGM Biopharmaceuticals. ARN receives Consultant Editor Compensation: JCO Precision Oncology. Consulting/Advisory Board: Foundation Med. ARN reports Travel Compensation from: SITC/ AACR/ Conquer Cancer Foundation, Jazz Pharmaceuticals, Binay Tara Foundation, Foundation Med Funding: None., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Introduction: Tarlatamab demonstrated a durable response and promising survival outcomes in patients with previously treated small cell lung cancer (SCLC) in the phase 2, open-label DeLLphi-301 trial. Patient-reported outcomes (PROs) were evaluated to assess the benefit-risk profile of tarlatamab., Methods: Patients received tarlatamab intravenously every 2 weeks at a dose of 10 mg (regulatory approved dose) or 100-mg until progression or loss of benefit. PROs, including European Organization for Research and Treatment of Cancer 30-item Quality of Life Questionnaire (EORTC-QLQ-C30) and 13-item lung cancer module (LC13), Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and the GP5 question of the Functional Assessment of Cancer Therapy - General Form (FACT-GP5), were collected at Cycle 1 (days 1, 8, 22), Cycle 2 (days 1, 15) and every 6 weeks from Cycle 3 onwards. PROs were summarized descriptively alongside the amount and reason for missing data and analyzed using a mixed model for repeated measures. In addition, median time to deterioration (TTD) for symptom and functional scales was analyzed., Results: A total of 100 patients were PRO-evaluable at the selected target dose (10 mg). EORTC-QLQ-C30 and LC13 completion rates (proportion of PRO assessments expected to be completed) were high (> 80%) throughout the study. Least square mean changes from baseline showed a trend towards improvement for the QLQ-C30 subscale of global health status and stabilization for physical functioning. Patients experienced reduced symptom burden for dyspnea which was more pronounced for patients at later cycles (≥ 10 points), and stabilization for chest pain and cough. Median TTD exceeded 6 months for cough and dyspnea and was not estimable for chest pain. Overall, tarlatamab was well tolerated with the majority of patients reporting no bother or a little bit of bother from side effects post baseline. Patient-reported adverse events were generally of mild to moderate severity occurring rarely or occasionally., Conclusion: Alongside previously reported antitumor activity, tarlatamab demonstrated a positive benefit-risk profile in previously treated SCLC with favorable PROs across a range of functional outcomes and symptoms, while showing manageable and sustained tolerability., Gov Number: NCT05060016., Competing Interests: Declarations. Conflict of Interest: Horst-Dieter Hummel reports consultancy work and steering board membership, support for attending meetings, and participation on a data safety monitoring board with Amgen. Myng-Ju Ahn received consultancy fees from Amgen, Astra-Zeneca, Daiichi-Sankyo, Eli Lilly, F. Hoffman-La-Roche, Merck, Merck KGaA, and is employed as a professor of the Samsung Medical Centre. Fiona Blackhall reports consulting fees and payment or honoraria from Amgen and AstraZeneca. Martin Reck has been a paid member speaker bureau and/or consultant for Amgen, AstraZeneca AB, BeiGene USA Inc, Boehringer Ingelheim, Bristol Myers Squibb Company, Daiichi Sankyo Company LTD Eli Lilly F. Hoffmann-La Roche, GlaxoSmithKline, Merck Sharp and Dohme, Pfizer, Regeneron Pharmaceuticals, and conducted Data and Safety Monitoring for Sanofi. Hiroaki Akamatsu received honoraria from Amgen Inc, AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Eli Lilly Japan K.K., MSD K.K., Nippon Kayaku Co. Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd., Pfizer Inc, Takeda Pharmatheutical Co. Ltd. and Taiho Pharmaceutical Co. Ltd.. He served as an advisor role for Amgen Inc, Janssen Pharmaceutical K.K., and Sandoz. He received research funding from Amgen Inc, Chugai Pharmaceutical Co. Ltd., and MSD K.K. Suresh Ramalingan reports consultancy fees from Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKine, Merck, Takeda Oncology. Hossein Borghaei reports research support (Clinical Trials) from BMS, Lilly, Amgen; Advisory16 Board/Consultant role for BMS, Lilly, Genentech, Pfizer, Merck, EMD-Serono, Boehringer Ingelheim, Astra Zeneca, Novartis, Genmab, Regeneron, BioNTech, Amgen, Axiom, PharmaMar, Takeda, Mirati, Daiichi, Guardant, Natera, Oncocyte, Beigene, iTEO, Jazz, Janssen, DaVolterra; Data and Safety Monitoring Board participation with University of Pennsylvania: CAR T Program, Takeda, Incyte, Novartis; employment with Fox Chase Cancer Center; Scientific Advisory Board participation with Sonnetbio (Stock Options); Inspirna (formerly Rgenix, Stock Options); Nucleai (stock options); Honoraria from Amgen, Pfizer, Daiichi, Regeneron; Travel support from Amgen, BMS, Merck, Lilly, EMD-Serono, Genentech, Regeneron. Melissa Johnson reports a grant or contract for research on behalf of AbbVie, Acerta Pharma, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array Biopharma, ArriVent BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAtla, Black Diamond, Boehringer Ingelheim, Calithera Biosciences, Carisma Therapeutics, Checkpoint Therapeutics, City of Hope National Medical Center, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo Company, Dracen Pharmaceuticals, Dynavax Technologies, Eli Lilly and Company, Elicio Therapeutics, EMD Serono, EQRx, Erasca, Exelixis, Fate Therapeutics, Genentech USA, Inc, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchinson MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunitas Therapeutics, Immunocore, Incyte Corporation, Janssen Research & Development, LLC, Jounce Therapeutics, Kadmon Pharmaceuticals LLC, Kartos Therapeutics, LockBody Therapeutics, Loxo Oncology, Lycera, Memorial Sloan-Kettering Cancer Center, Merck, Merus, Mirati Therapeutics, Mythic Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceutical, Palleon Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Rain Therapeutics, RasCal Therapeutics, Regeneron Pharmaceuticals, Inc, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, SANOFI US SERVICES INC, Seven and Eight Bipharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem Centrx, Syndax Pharmaceuticals, Takeda Pharmaceuticals America, Inc, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, WindMIL Therapeutics, Y-mAbs Therapeutics, Melissa Johnson also reports consultancy fees from AbbVie, Amgen, Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera Biosciences, D3 Bio Limited, Daiichi Sankyo Company, EcoR1, Fate Therapeutics, Genentech USA, Inc, Genmab, Genocea Biosciences, Gilead Sciences, Inc, GlaxoSmithKline, Gritstone Oncology, IDEAYA Biosciences, Immunocore, Janssen Research & Development, LLC, Jazz Pharmaceuticals Inc, Merck, Mirati Therapeutics, Molecular Axiom, Normunity, Pyramid Biosciences, Regeneron Pharmaceuticals, Revolution Medicines, SANOFI-AVENTIS U.S. LLC, Seagen Inc, Synthekine, Takeda Pharmaceutical Company, and VBL Therapeutics. Franziska Dirnberger is an employee of Amgen and owns Amgen stocks. Kim Cocks is an employee of Adelphi Values who received consultancy fees for the conduct of the analyses and medical writing. Shuang Huang is an employee of Amgen and owns Amgen stocks. Sujoy Mukherjee is an employee of Amgen and owns Amgen stocks. Luis Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, Beigene, Daiichi, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme Corp, BMS, Janssen-Cilag International25 NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Other, Member: AACR, ASCO, ESMO; Financial Interests, Other, Foundation Board Member: AECC; Financial Interests, Other, President: ASEICA (Spanish Association of Cancer Research); Financial Interests, Other, Foundation President: ONCOSUR; Financial Interests, Other, member: Small Lung Cancer Group. Ethical Approval: The trial was conducted in accordance with the International Council for Harmonisation Good Clinical Practice guidelines and the principles of the Declaration of Helsinki (WCG (approval number 20233898). The protocol and amendments were approved by the institutional review board at each participating site and by regulatory authorities in the participating countries. All the patients provided written informed consent. A data-review team external to the trial team provided oversight of safety throughout the trial., (© 2025. The Author(s).)

Permeability is an important molecular property in drug discovery, as it co-determines pharmacokinetics whenever a drug crosses the phospholipid bilayer, e.g., into the cell, in the gastrointestinal tract, or across the blood-brain barrier. Many methods for the determination of permeability have been developed, including cell line assays (CACO-2 and MDCK), cell-free model systems like parallel artificial membrane permeability assay (PAMPA) mimicking, e.g., gastrointestinal epithelia or the skin, as well as the black lipid membrane (BLM) and submicrometer liposomes. Furthermore, many in silico approaches have been developed for permeability prediction: meta-analysis of publicly available databases for permeability data (MolMeDB and ChEMBL) was performed to establish their usability. Four experimental and two computational methods were evaluated. It was shown that repeatability of the reported permeability measurement is not great even for the same method. For the PAMPA method, two different permeabilities are reported: intrinsic and apparent. They can vary in degrees of magnitude; thus, we suggest being extra cautious using literature data on permeability. When we compared data for the same molecules using different methods, the best agreement was between cell-based methods and between BLM and computational methods. Existence of unstirred water layer (UWL) permeability limits the data agreement between cell-based methods (and apparent PAMPA) with data that are not limited by UWL permeability (computational methods, BLM, intrinsic PAMPA). Therefore, different methods have different limitations. Cell-based methods provide results only in a small range of permeabilities (-8 to -4 in cm/s), and computational methods can predict a wider range of permeabilities beyond physical limitations, but their precision is therefore limited. BLM with liposomes can be used for both fast and slow permeating molecules, but its usage is more complicated than standard transwell techniques. To sum up, when working with in-house measured or published permeability data, we recommend caution in interpreting and combining them.

The emission control of harmful compounds and greenhouse gases and the development of alternative, sustainable fuel sources is a major focus in current research. A solution for this problem lies in the development of efficient catalytic materials. Here, gas phase model systems represent prominent examples for obtaining fundamental insights on reaction properties of prospective catalytic systems. In this work, we review results from studies of tantalum clusters and their oxides in the gas phase and discuss insights with a potential relevance for applied systems. We focus on reactions that are essential for sustainable chemistry in the future. In detail, we address the activation of methane, which may enable the transformation of a greenhouse gas to a chemical feedstock, and we discuss the activation of NH 3 , which may function as an alternative energy carrier whose unwanted emission needs to be curbed in future applications. Finally, we consider the activation of N 2 as a third reaction, since reducing the high energy demand of ammonia synthesis still bears significant challenges. While tantalum may be an interesting catalytic material, the discussed studies may also serve as benchmark for investigations of other materials., (© 2024 The Authors. ChemPhysChem published by Wiley-VCH GmbH.)