Ikerbasque

Diagnostic delay is common in pediatric inflammatory bowel disease (PIBD), and fecal calprotectin (FCP) is often limited by challenges with sample collection. Therefore, we aimed to identify and validate a blood-based diagnostic protein signature of PIBD. Proteins were analyzed using proximity extension assay in plasma samples from treatment-naïve pediatric patients in a Swedish inception cohort referred for suspected inflammatory bowel disease (IBD) and validated in an independent Norwegian population-based pediatric inception cohort. Diagnostic performance was estimated by the area under the curve (AUC) with 95% confidence intervals (CIs). The discovery cohort included 58 patients with PIBD and 36 symptomatic controls without evidence of IBD, while the validation cohort consisted of 79 patients with PIBD and 37 symptomatic controls. In total, 154 proteins were examined. Univariable analyses identified 26 differentially regulated proteins for PIBD versus symptomatic controls in the discovery cohort (q < 0.05), whereas 29 proteins were differentially regulated in the validation cohort. Using regularized logistic regression, we identified a diagnostic model of 31 proteins that differentiated PIBD from symptomatic controls in the discovery cohort (AUC = 0.83; 95% CI: 0.74-0.90). The protein signature was further reduced to a clinically relevant biomarker consisting of high-sensitivity C-reactive protein (hsCRP) and seven other proteins with diagnostic capacity (AUC = 0.85, 95% CI: 0.78-0.92) outperforming hsCRP in the validation cohort (p = 0.006). We identified and validated a blood-based protein signature for PIBD with superior diagnostic performance compared to hsCRP. Given the challenges of fecal sample collection, further assay development may enable integration of these biomarkers into diagnostic pathways for PIBD. ClinicalTrials.gov identifier: NCT02727959.

Cancer dormancy refers to an asymptomatic stage in cancer progression that contains residual disease. Cancer cells can disseminate from early tumors even before they are detectable, from advanced tumors, and from other metastases. Thus, cancer dormancy is a collective phenomenon, composed of single dormant cells that stopped dividing, tumor mass dormancy where cell proliferation is balanced by cell death, and active micrometastases. Dormancy evolves with complex spatiotemporal dynamics across length scales (from cell-intrinsic to cell-extrinsic interactions and microenvironmental regulation up to the body-wide systemic level) and across timescales (from single dormant cells to dormant tumor masses and active micrometastases), each responding differently to fluctuating microenvironments. Here we review biological in vivo and clinical observations of breast cancer dormancy across scales in length and time. Next, we outline 3D bioengineered models in which these different spatial and temporal scales are considered. Finally, we discuss challenges and opportunities of incorporating patient-derived cells. Collective cell behavior is an important aspect in cancer progression and, as such, modeling dormancy across scales in length and time could open new avenues to help us understand and predict the transition to active metastatic growth.

Brain aging consists of a progressive loss of functional capacities, which is associated with a progressive cognitive decline and can lead to neurodegenerative diseases. Studies comparing the underlying molecular mechanisms of the human hippocampus between young and older adults remain scarce. In our study, we completed a transcriptomic analysis from hippocampal samples of different ages and performed 2 complementary analyses. A comparison between young and old groups revealed a set of genes differentially expressed in aged individuals linked to inflammation and immune system pathways, DNA repair, metabolism, or neural activity. Correlation analysis showed that the expression of an additional subset of 6 genes was associated with chronological aging. Among them, further analysis identified RAD23B as the most significant gene with a negative correlation of its mRNA and protein expression with age in the human hippocampus. Its expression was even lower in patients with Alzheimer's disease. RAD23B was mostly expressed in neurons and astrocytes, where studies in human primary cultures uncovered that it is required for cell survival and function. In summary, these results unravel dynamic gene expression changes that distinguish young from older adults and identify RAD23B as a putative biomarker and regulator of cell aging in the brain.

ABSTRACTIn this work, we developed biodegradable cellulose acetate (CA) fibers infiltrated with ZnO nanocrystals for the Acne vulgaris (AV) treatment. The antibacterial effect (through Zn2+ release) was activated upon oxygen plasma treatment. CA fibers (fiber diameter ≈ 2 µm) were produced via centrifugal spinning, followed by ZnO infiltration (up to 8 wt% of Zn content) using Vapor Phase Infiltration (VPI) with varying deposition cycles. As CA fibers are naturally hydrophobic, oxygen plasma treatment was applied to turn them hydrophilic and to improve skin wetting. The combination of these steps is presented for the first time. Plasma treatment introduced oxygen‐containing functional groups on the CA surface, significantly improving wettability. Scanning electron microscopy analyses of treated fibers showed no morphological damage. Detailed characterization (using X‐ray photoelectron spectroscopy, Raman spectroscopy, energy dispersive X‐ray fluorescence, X‐ray diffraction, tranmission electron microscopy) focused on fibers with 32 and 128 VPI cycles, revealed that plasma partially oxidized and etched the surface, affecting the ZnO distribution. Plasma‐modified fibers, unlike untreated ones, exhibited antibacterial activity against AV‐causing bacteria (Cutibacterium acnes and Staphylococcus epidermidis), creating significant inhibition zones (up to 5 mm), demonstrating their potential as promising therapeutic modality. Overall, plasma treatment enabled effective surface functionalization, producing antibacterial fibers with enhanced surface properties suitable for application in AV management.

CeTe3 is a 2-dimensional (2D) Van der Waals (VdW) material with incommensurate charge density waves (CDW), extremely high transition temperature (TCDW), and a large momentum-dependent CDW gap that leaves a significant portion of the Fermi surface intact. It is also considered to be a weak Kondo system, a property unexpected for a material with incommensurate CDW, where each atomic site is slightly different. Here, we study the properties of the CDW state in several RTe3 (R is rare earth) materials and examine the hybridization of itinerant states with the localized Ce 4f multiplet in CeTe3 by using angle resolved photoemission spectroscopy. We find that the renormalization of the itinerant states originating from the hybridization with the deeper localized 4f states at −260 meV is k−dependent and extends to the Fermi level. As these localized states are far from the Fermi level, the observed hybridization affects the effective masses only marginally and does not lead to heavy fermions. However, since the same renormalizing mechanism normally leads to the heavy fermion physics when the localized 4f states are near the Fermi level, our observation of its strong k−dependence suggests that this could be the reason for discrepancy between the heavy masses in specific heat and light ones in Shubnikov de Haas oscillations, often observed in heavy fermions.

Polymorphism in polyarenes significantly impacts their applications, yet remains underexplored in curved species like corannulene. To this end, we utilised fast scanning calorimetry and X-ray diffraction to explore its stability regimes. Unlike its flat counterpart perylene, corannulene exhibits a glass transition at Tg=323 K when cooled from the melt at rates exceeding -500 K s-1. Upon heating, three thermal events at ca. 380, 430, and 500 K reveal hitherto unknown polymorphs. Diffraction data link these transitions to well-defined and thermally activated rotations within the crystal, inducing a sharp density decrease matching Tg. These changes are accompanied by abnormal atomic displacement parameters. Unlike flat polyarenes of a similar molecular size, the diffraction data also provide strong evidence that this solid ought to be regarded as two distinctly different materials below and above Tg. Altogether, our findings bring to the fore the unanticipated complexity underpinning the structure and thermodynamic response of solid corannulene, the simplest geodesic polyarene.

ABSTRACT Polaritonic crystals for hyperbolic phonon‐polaritons (PhP) in van der Waals materials are burdened by the intermode scattering due to the inherently multimodal nature of PhP. So far, polaritonic crystals have been demonstrated within the Type‐II Reststrahlen band (RB‐II) where the in‐plane components of the dielectric permittivity tensor are negative, while the out‐of‐plane component is positive. By contrast, a Type‐I Reststrahlen band (RB‐I) is characterized by the negative out‐of‐plane and positive in‐plane permittivity, and consequently, the inversion of PhP field symmetry, negative phase velocity, and anomalous dispersion. Such an operation regime remains unexplored for periodic structures supporting collective polaritonic modes. Here, we employ a biaxial crystal α‐MoO 3 and near‐field imaging to study mid‐infrared polaritonic Bloch modes in a 1‐D Fourier crystal within the RB‐I. Surprisingly, we observe a manifestation of Bloch waves as a dispersionless near‐field pattern across the first Brillouin zone, in contrast to previous works exclusively focused on the RB‐II. Our results demonstrate the possibility to realize a quasi‐single‐mode operation regime of polaritonic crystal for the inherently multimode hyperbolic PhP, and reveal the importance of field symmetry for polaritonic crystals in general and for the emerging field of Fourier crystals in particular, promising new ways to manipulate the nanolight.

ABSTRACT The enigmatic Little Red Dots (LRDs) discovered by the James Webb Space Telescope (JWST) exhibit properties challenging their interpretation as common galaxies or active galactic nuclei (AGNs). Understanding their nature is key to placing them within our picture of early galaxy and massive black hole (MBH) evolution. To this aim, we build a realistic comparison between LRD observations with photometric properties of galaxies and AGN simulated by the L-GalaxiesBH model in a NIRCam mock sky. We model stellar continua and emission lines, the MBH emission from accretion disc, infrared radiation from dusty torus, and lines from narrow and broad-line regions, accounting for dust attenuation and obscuration. Using realistic photometric cuts, we select a population of LRDs including both AGN and galaxies. The LRD fraction peaks at 40 per cent ($\sim 10^{-4}\rm Mpc^{-3}$) at $z\sim 4$. Our LRDs are central galaxies spanning $M_\star =10^8{\!-\!}10^{10.5}\rm M_\odot$. A population of galaxies with $M_\star \lt 10^9\rm M_\odot$ appear as LRDs due to older stellar populations. At higher masses, LRDs dominate the halo and stellar mass functions ($M_{\rm vir} \gt 10^{11.5}\rm M_\odot$, $M_\star \gt 10^{9.5}\rm M_\odot$), and the interplay between AGN and galaxy emission drives the LRD selection. AGN dominate rest-frame UV-optical emission, while dust obscuration is secondary. LRDs host lighter MBHs ($\sim 10^{6.5}\rm M_\odot$) than non-LRDs ($\sim 10^{7.5}\rm M_\odot$), with fainter emission unable to balance their hosts Balmer breaks. We find no evidence for dominant heavy-seed origin of MBHs. LRD Galaxies (97 per cent hosting MBHs) and LRD AGNs are disc-dominated, with LRD AGNs showing larger bulges formed mainly via disc instabilities.