Dynamics of Gene Expression Profiling and Identification of High-Risk Patients for Severe COVID-19.

The clinical manifestations of SARS-CoV-2 infection vary widely, from asymptomatic infection to the development of acute respiratory distress syndrome (ARDS) and death. The host response elicited by SARS-CoV-2 plays a key role in determining the clinical outcome. We hypothesized that determining the dynamic whole blood transcriptomic profile of hospitalized adult COVID-19 patients and characterizing the subgroup that develops severe disease and ARDS would broaden our understanding of the heterogeneity in clinical outcomes. We recruited 60 hospitalized patients with RT-PCR-confirmed SARS-CoV-2 infection, among whom 19 developed ARDS. Peripheral blood was collected using PAXGene RNA tubes within 24 h of admission and on day 7. There were 2572 differently expressed genes in patients with ARDS at baseline and 1149 at day 7. We found a dysregulated inflammatory response in COVID-19 ARDS patients, with an increased expression of genes related to pro-inflammatory molecules and neutrophil and macrophage activation at admission, in addition to an immune regulation loss. This led, in turn, to a higher expression of genes related to reactive oxygen species, protein polyubiquitination, and metalloproteinases in the latter stages. Some of the most significant differences in gene expression found between patients with and without ARDS corresponded to long non-coding RNA involved in epigenetic control.

Spatial magnetic imaging of non-axially symmetric vortex domains in cylindrical nanowire by transmission X-ray microscopy.

The spatial magnetization texture of a cylindrical nanowire has been determined by Transmission X-ray Microscopy (TXM) and X-ray magnetic circular dichroism (XMCD). For this purpose, nanowires with designed geometry, consisting of CoNi/Ni periodic segments, have been grown by designed electrodeposition into alumina templates. Experimental data allow one to conclude the presence of mono- and trivortex magnetic domains in CoNi segments but, unusually, these states are characterized by an asymmetric XMCD contrast across the nanowire's section. Micromagnetic modelling shows non-trivial three-dimensional structures with ellipsoidal vortex cores and non-axially symmetric magnetization along the nanowire direction. The modelled TXM contrast of micromagnetic structures allows to correlate the experimental asymmetric XMCD contrast to the easy axis direction of the uniaxial magnetocrystalline anisotropy.

Two-Step Resist Deposition of E-Beam Patterned Thick Py Nanostructures for X-ray Microscopy.

Patterned elements of permalloy (Py) with a thickness as large as 300 nm have been defined by electron beam lithography on X-ray-transparent 50 nm thick membranes in order to characterize their magnetic structure via Magnetic Transmission X-ray Microscopy (MTXM). To avoid the situation where the fragility of the membranes causes them to break during the lithography process, it has been found that the spin coating of the resist must be applied in two steps. The MTXM results show that our samples have a central domain wall, as well as other types of domain walls, if the nanostructures are wide enough.

Creation and observation of Hopfions in magnetic multilayer systems.

Among topological solitons, magnetic skyrmions are two-dimensional particle-like objects with a continuous winding of the magnetization, and magnetic Hopfions are three-dimensional objects that can be formed from a closed loop of twisted skyrmion strings. Theoretical models suggest that magnetic Hopfions can be stabilized in frustrated or chiral magnetic systems, and target skymions can be transformed into Hopfions by adapting their perpendicular magnetic anisotropy, but their experimental verification has been elusive so far. Here, we present an experimental study of magnetic Hopfions that are created in Ir/Co/Pt multilayers shaped into nanoscale disks, known to host target skyrmions. To characterize three-dimensional spin textures that distinguish Hopfions from target skyrmions magnetic images are recorded with surface-sensitive X-ray photoemission electron microscopy and bulk-sensitive soft X-ray transmission microscopy using element-specific X-ray magnetic circular dichroism effects as magnetic contrast. These results could stimulate further investigations of Hopfions and their potential application in three-dimensional spintronics devices.

Helical surface magnetization in nanowires: the role of chirality.

Nanomagnetism is nowadays expanding into three dimensions, triggered by the discovery of new magnetic phenomena and their potential use in applications. This shift towards 3D structures should be accompanied by strategies and methodologies to map the tridimensional spin textures associated. We present here a combination of dichroic X-ray transmission microscopy at different angles and micromagnetic simulations allowing to determine the magnetic configuration of cylindrical nanowires. We have applied it to permalloy nanowires with equispaced chemical barriers that can act as pinning sites for domain walls. The magnetization at the core is longitudinal and generates at the surface of the wire helical magnetization. Different types of domain walls are found at the pinning sites, which respond differently to applied fields depending on the relative chirality of the adjacent domains.

Artificial Double-Helix for Geometrical Control of Magnetic Chirality.

Chirality plays a major role in nature, from particle physics to DNA, and its control is much sought-after due to the scientific and technological opportunities it unlocks. For magnetic materials, chiral interactions between spins promote the formation of sophisticated swirling magnetic states such as skyrmions, with rich topological properties and great potential for future technologies. Currently, chiral magnetism requires either a restricted group of natural materials or synthetic thin-film systems that exploit interfacial effects. Here, using state-of-the-art nanofabrication and magnetic X-ray microscopy, we demonstrate the imprinting of complex chiral spin states via three-dimensional geometric effects at the nanoscale. By balancing dipolar and exchange interactions in an artificial ferromagnetic double-helix nanostructure, we create magnetic domains and domain walls with a well-defined spin chirality, determined solely by the chiral geometry. We further demonstrate the ability to create confined 3D spin textures and topological defects by locally interfacing geometries of opposite chirality. The ability to create chiral spin textures via 3D nanopatterning alone enables exquisite control over the properties and location of complex topological magnetic states, of great importance for the development of future metamaterials and devices in which chirality provides enhanced functionality.

3D reconstruction of magnetization from dichroic soft X-ray transmission tomography.

The development of magnetic nanostructures for applications in spintronics requires methods capable of visualizing their magnetization. Soft X-ray magnetic imaging combined with circular magnetic dichroism allows nanostructures up to 100-300 nm in thickness to be probed with resolutions of 20-40 nm. Here a new iterative tomographic reconstruction method to extract the three-dimensional magnetization configuration from tomographic projections is presented. The vector field is reconstructed by using a modified algebraic reconstruction approach based on solving a set of linear equations in an iterative manner. The application of this method is illustrated with two examples (magnetic nano-disc and micro-square heterostructure) along with comparison of error in reconstructions, and convergence of the algorithm.

Design and performance of BOREAS, the beamline for resonant X-ray absorption and scattering experiments at the ALBA synchrotron light source.

The optical design of the BOREAS beamline operating at the ALBA synchrotron radiation facility is described. BOREAS is dedicated to resonant X-ray absorption and scattering experiments using soft X-rays, in an unusually extended photon energy range from 80 to above 4000 eV, and with full polarization control. Its optical scheme includes a fixed-included-angle, variable-line-spacing grating monochromator and a pair of refocusing mirrors, equipped with benders, in a Kirkpatrick-Baez arrangement. It is equipped with two end-stations, one for X-ray magnetic circular dichroism and the other for resonant magnetic scattering. The commissioning results show that the expected beamline performance is achieved both in terms of energy resolution and of photon flux at the sample position.

MISTRAL: a transmission soft X-ray microscopy beamline for cryo nano-tomography of biological samples and magnetic domains imaging.

The performance of MISTRAL is reported, the soft X-ray transmission microscopy beamline at the ALBA light source (Barcelona, Spain) which is primarily dedicated to cryo soft X-ray tomography (cryo-SXT) for three-dimensional visualization of whole unstained cells at spatial resolutions down to 30 nm (half pitch). Short acquisition times allowing for high-throughput and correlative microscopy studies have promoted cryo-SXT as an emerging cellular imaging tool for structural cell biologists bridging the gap between optical and electron microscopy. In addition, the beamline offers the possibility of imaging magnetic domains in thin magnetic films that are illustrated here with an example.

The ALBA spectroscopic LEEM-PEEM experimental station: layout and performance.

The spectroscopic LEEM-PEEM experimental station at the CIRCE helical undulator beamline, which started user operation at the ALBA Synchrotron Light Facility in 2012, is presented. This station, based on an Elmitec LEEM III microscope with electron imaging energy analyzer, permits surfaces to be imaged with chemical, structural and magnetic sensitivity down to a lateral spatial resolution better than 20 nm with X-ray excited photoelectrons and 10 nm in LEEM and UV-PEEM modes. Rotation around the surface normal and application of electric and (weak) magnetic fields are possible in the microscope chamber. In situ surface preparation capabilities include ion sputtering, high-temperature flashing, exposure to gases, and metal evaporation with quick evaporator exchange. Results from experiments in a variety of fields and imaging modes will be presented in order to illustrate the ALBA XPEEM capabilities.

Developments in optics and performance at BL13-XALOC, the macromolecular crystallography beamline at the ALBA synchrotron.

BL13-XALOC is currently the only macromolecular crystallography beamline at the 3 GeV ALBA synchrotron near Barcelona, Spain. The optics design is based on an in-vacuum undulator, a Si(111) channel-cut crystal monochromator and a pair of KB mirrors. It allows three main operation modes: a focused configuration, where both mirrors can focus the beam at the sample position to 52 µm × 5.5 µm FWHM (H × V); a defocused configuration that can match the size of the beam to the dimensions of the crystals or to focus the beam at the detector; and an unfocused configuration, where one or both mirrors are removed from the photon beam path. To achieve a uniform defocused beam, the slope errors of the mirrors were reduced down to 55 nrad RMS by employing a novel method that has been developed at the ALBA high-accuracy metrology laboratory. Thorough commissioning with X-ray beam and user operation has demonstrated an excellent energy and spatial stability of the beamline. The end-station includes a high-accuracy single-axis diffractometer, a removable mini-kappa stage, an automated sample-mounting robot and a photon-counting detector that allows shutterless operation. The positioning tables of the diffractometer and the detector are based on a novel and highly stable design. This equipment, together with the operation flexibility of the beamline, allows a large variety of types of crystals to be tackled, from medium-sized crystals with large unit-cell parameters to microcrystals. Several examples of data collections measured during beamline commissioning are described. The beamline started user operation on 18 July 2012.

[Effectiveness of endovascular prostheses as initial treatment for superior vena cava syndrome of malignant cause]. / Tratamiento inicial del síndrome de vena cava superior de causa neoplásica mediante endoprótesis.

BACKGROUND AND OBJECTIVE: Superior vena cava syndrome (SVCS) is caused by venous return obstruction often originated by an invading mediastinal tumour. Our objective was to evaluate the usefulness of stents as initial treatment for SVCS of malignant origin. PATIENTS AND METHODS: From December 1996 to August 2010, 120 patients with SVCS were referred for percutaneous treatment. Seventy-six were under oncological follow-up cases and in 44 cases the tumour was unknown. A non-concurrent prospective study was made of 113 patients without prior chemotherapy or radiotherapy, who opted for endovascular treatment as first option. RESULTS: One hundred and two men and 11 women were treated, mean age 61.18 years old (range 45-85). SVCS causes included lung cancer (100), lung metastases (6), compression by enlarged lymph nodes (6), and an embryonic tumour. One hundred and fifty-five prostheses were implanted. One stent was enough in 75 patients, 2 stents in 34, and 3 in 4. Technical success rate was 98.2%. Symptoms disappeared completely in 97 patients and partially in 13. Complications were stent migration (5), epistaxis (1), and post-procedure groin hematoma (1). Seventy-three asymptomatic patients had a mean survival of 210 days (75% primary permeability and 52.9% secondary permeability). CONCLUSIONS: The use of stents in malignant SVCS is a safe and effective procedure for venous obstruction, leading to the immediate disappearance of symptoms, allowing the underlying tumour staging, facilitating the establishment of the best treatment and improving life quality.

Design and construction of multicrystal analyser detectors using Rowland circles: application to MAD26 at ALBA.

A concept is given for describing multicrystal analyser detectors (MADs), as they are in use for synchrotron powder diffraction, on the basis of the Rowland circle construction. The Rowland circle is typically used to describe focusing geometries and can be adapted for the case of MADs working at a single energy as well as in a limited energy range. With this construction it is also possible to quantify and optimize the walk of the beam along non-central crystals which is inevitable in certain detector designs. The results of this geometrical inspection are correlated with a real detector design that is implemented at the ALBA synchrotron facility in Spain. An error budget is given to estimate the influence and amount of tolerance of the manufacturing process.

The role of steps in surface catalysis and reaction oscillations.

Atomic steps at the surface of a catalyst play an important role in heterogeneous catalysis, for example as special sites with increased catalytic activity. Exposure to reactants can cause entirely new structures to form at the catalyst surface, and these may dramatically influence the reaction by 'poisoning' it or by acting as the catalytically active phase. For example, thin metal oxide films have been identified as highly active structures that form spontaneously on metal surfaces during the catalytic oxidation of carbon monoxide. Here, we present operando X-ray diffraction experiments on a palladium surface during this reaction. They reveal that a high density of steps strongly alters the stability of the thin, catalytically active palladium oxide film. We show that stabilization of the metal, caused by the steps and consequent destabilization of the oxide, is at the heart of the well-known reaction rate oscillations exhibited during CO oxidation at atmospheric pressure.

Ultraflex precision colonic stent placement as a bridge to surgery in patients with malignant colon obstruction.

BACKGROUND: Emergency surgery for malignant colon obstruction entails relatively high morbidity and mortality rates and typically necessitates a 2-step resection. These problems might be potentially mitigated by placement of a self-expanding metal stent (SEMS) as a bridge to surgery. A nitinol colorectal SEMS may offer several advantages, but available evidence on the utility of this SEMS type remains highly limited. OBJECTIVE: Our purpose was to evaluate the effectiveness and safety as a bridge to surgery of a nitinol SEMS designed for colorectal use. DESIGN: Prospective and retrospective multicenter clinical study. SETTING: Sixteen European study centers. PATIENTS: Thirty-six patients with malignant colonic obstruction. INTERVENTIONS: Nitinol colorectal SEMS placement. MAIN OUTCOME MEASURES: Technical success in accurate SEMS placement with coverage of the entire stricture length, clinical success in alleviating colonic obstructive symptoms, and bridging to elective surgery. RESULTS: Technical success was achieved in 97% of patients with a 95% CI of 85% to 100% and clinical success in 81% (95% CI, 64%-92%). Elective surgery was performed in 94% (95% CI, 81%-99%) of patients at a median of 11 days (95% CI, 7-15 days) after SEMS placement. SEMS-related perforation occurred in 3 patients. LIMITATIONS: No control group was included in this nonrandomized cohort study. CONCLUSIONS: In this first comparatively large clinical study of a nitinol colorectal SEMS as a bridge to surgery, a high proportion of patients successfully proceeded to elective surgery after prior decompression by SEMS placement.

[Radiation therapy with synchrotron radiation and cisplatin-based chemotherapy as a treatment of gliomas]. / Aplicación de la radioterapia con radiación sincrotrón y de la quimioterapia con cisplatino en el tratamiento de los gliomas cerebrales.

The application of synchrotron radiation in medicine dates back to more than one decade. In particular, a team of researchers led by Dr. F. Esteve has been working for several years in the Grenoble Synchrotron (ESRF) on radiotherapy treatments to heal brain tumors. The team has recently obtained a very promising new result. Gliomas the commonest brain tumor in the adult and the mean survival in advanced disease patients is lower than one year. Conventional radiation therapy is used palliatively since it is one of the most radiotherapy-resistant tumors. Moreover, chemotherapy and surgery have no utility in most cases. Experiments at the Grenoble Synchrotron have been carried out in mice with gliomas and they consist of injecting cysplatine into the tumors so that an intense monochromatic radiation is applied afterwards. Half-life of sick untreated mice is 28 days. With the use of cysplatine alone, it expands to 48 days. However, the association of two treatments supposes a half-life of 206 days (six times greater than in untreated mice). After one year of treatment, 34% of animals remain alive, which constitutes a result never seen before in this type of radio-resistant tumors.

The role of intermolecular and molecule-substrate interactions in the stability of alkanethiol nonsaturated phases on Au(111).

The structure and stability of alkanethiols self-assembled on Au(111) have been studied as a function of the molecular chain length by means of atomic force microscopy (AFM) and grazing incidence X-ray diffraction (GIXD). Below saturation, phases consisting of molecules with different tilt angles and periodicities are formed. Differences in the mechanical stability of these phases are revealed by AFM experiments and discussed in terms of the competition between intermolecular and molecule-substrate interactions as a function of chain length. For long molecules, intermolecular interactions play a dominant role which stabilizes the formation of closed packed 30 degrees tilted ( radical 3x radical 3)R30 degrees structures. For short molecules, the van der Waals interaction with the gold substrate favors the formation of a 50 degrees tilted phase in which the molecules are arranged in a rectangular configuration.

Expression of myeloid-specific genes in childhood acute lymphoblastic leukemia - a cDNA array study.

Several specific cytogenetic changes are known to be associated with childhood acute lymphoblastic leukemia (ALL), and many of them are important prognostic factors for the disease. Little is known, however, about the changes in gene expression in ALL. Recently, the development of cDNA array technology has enabled the study of expression of hundreds to thousands of genes in a single experiment. We used the cDNA array method to study the gene expression profiles of 17 children with precursor-B ALL. Normal B cells from adenoids were used as reference material. We discuss the 25 genes that were most over-expressed compared to the reference. These included four genes that are normally expressed only in the myeloid lineages of the hematopoietic cells: RNASE2, GCSFR, PRTN3 and CLC. We also detected over-expression of S100A12, expressed in nerve cells but also in myeloid cells. In addition to the myeloid-specific genes, other over-expressed genes included AML1, LCP2 and FGF6. In conclusion, our study revealed novel information about gene expression in childhood ALL. The data obtained may contribute to further studies of the pathogenesis and prognosis of childhood ALL.